Proteoglycan-4 is correlated with longer survival in HCC patients and enhances sorafenib and regorafenib effectiveness via CD44 in vitro

Sorafenib and regorafenib administration is among the preferential approaches to treat hepatocellular carcinoma (HCC), but does not provide satisfactory benefits. Intensive crosstalk occurring between cancer cells and other multiple non-cancerous cell subsets present in the surrounding microenvironm...

Full description

Saved in:
Bibliographic Details
Published inCell death & disease Vol. 11; no. 11; p. 984
Main Authors Dituri, Francesco, Scialpi, Rosanna, Schmidt, Tannin A., Frusciante, Martina, Mancarella, Serena, Lupo, Luigi Giovanni, Villa, Erica, Giannelli, Gianluigi
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 16.11.2020
Springer Nature B.V
Subjects
13/1
13/106
13/109
13/31
13/51
13/95
38/109
38/77
631/67/1059/602
692/308/2778
Antibodies
Antineoplastic Combined Chemotherapy Protocols - pharmacology
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Biochemistry
Biomedical and Life Sciences
Carcinoma, Hepatocellular - drug therapy
Carcinoma, Hepatocellular - pathology
CD44 antigen
Cell adhesion & migration
Cell Biology
Cell Culture
Cell migration
Cell proliferation
Extracellular matrix
Fibroblasts
Hepatocellular carcinoma
Humans
Immunology
Inhibitor drugs
Life Sciences
Liver cancer
Liver Neoplasms - drug therapy
Liver Neoplasms - pathology
mRNA
Phenylurea Compounds - pharmacology
Phenylurea Compounds - therapeutic use
Proteoglycans
Proteoglycans - pharmacology
Proteoglycans - therapeutic use
Pyridines - pharmacology
Pyridines - therapeutic use
Sorafenib - pharmacology
Sorafenib - therapeutic use
Targeted cancer therapy
Transforming growth factor-b
Tumor Microenvironment
Online AccessGet full text
ISSN2041-4889
2041-4889
DOI10.1038/s41419-020-03180-8

Cover

Abstract Sorafenib and regorafenib administration is among the preferential approaches to treat hepatocellular carcinoma (HCC), but does not provide satisfactory benefits. Intensive crosstalk occurring between cancer cells and other multiple non-cancerous cell subsets present in the surrounding microenvironment is assumed to affect tumor progression. This interplay is mediated by a number of soluble and structural extracellular matrix (ECM) proteins enriching the stromal milieu. Here we assess the HCC tumor expression of the ECM protein proteoglycan 4 (PRG4) and its potential pharmacologic activity either alone, or in combination with sorafenib and regorafenib. PRG4 mRNA levels resulted strongly correlated with increased survival rate of HCC patients ( p  = 0.000) in a prospective study involving 78 HCC subjects. We next showed that transforming growth factor beta stimulates PRG4 expression and secretion by primary human HCC cancer-associated fibroblasts, non-invasive HCC cell lines, and ex vivo specimens. By functional tests we found that recombinant human PRG4 (rhPRG4) impairs HCC cell migration. More importantly, the treatment of HCC cells expressing CD44 (the main PRG4 receptor) with rhPRG4 dramatically enhances the growth-limiting capacity of sorafenib and regorafenib, whereas not significantly affecting cell proliferation per se. Conversely, rhPRG4 only poorly potentiates drug effectiveness on low CD44-expressing or stably CD44-silenced HCC cells. Overall, these data suggest that the physiologically-produced compound PRG4 may function as a novel tumor-suppressive agent by strengthening sorafenib and regorafenib effects in the treatment of HCC.
AbstractList Sorafenib and regorafenib administration is among the preferential approaches to treat hepatocellular carcinoma (HCC), but does not provide satisfactory benefits. Intensive crosstalk occurring between cancer cells and other multiple non-cancerous cell subsets present in the surrounding microenvironment is assumed to affect tumor progression. This interplay is mediated by a number of soluble and structural extracellular matrix (ECM) proteins enriching the stromal milieu. Here we assess the HCC tumor expression of the ECM protein proteoglycan 4 (PRG4) and its potential pharmacologic activity either alone, or in combination with sorafenib and regorafenib. PRG4 mRNA levels resulted strongly correlated with increased survival rate of HCC patients (p = 0.000) in a prospective study involving 78 HCC subjects. We next showed that transforming growth factor beta stimulates PRG4 expression and secretion by primary human HCC cancer-associated fibroblasts, non-invasive HCC cell lines, and ex vivo specimens. By functional tests we found that recombinant human PRG4 (rhPRG4) impairs HCC cell migration. More importantly, the treatment of HCC cells expressing CD44 (the main PRG4 receptor) with rhPRG4 dramatically enhances the growth-limiting capacity of sorafenib and regorafenib, whereas not significantly affecting cell proliferation per se. Conversely, rhPRG4 only poorly potentiates drug effectiveness on low CD44-expressing or stably CD44-silenced HCC cells. Overall, these data suggest that the physiologically-produced compound PRG4 may function as a novel tumor-suppressive agent by strengthening sorafenib and regorafenib effects in the treatment of HCC.Sorafenib and regorafenib administration is among the preferential approaches to treat hepatocellular carcinoma (HCC), but does not provide satisfactory benefits. Intensive crosstalk occurring between cancer cells and other multiple non-cancerous cell subsets present in the surrounding microenvironment is assumed to affect tumor progression. This interplay is mediated by a number of soluble and structural extracellular matrix (ECM) proteins enriching the stromal milieu. Here we assess the HCC tumor expression of the ECM protein proteoglycan 4 (PRG4) and its potential pharmacologic activity either alone, or in combination with sorafenib and regorafenib. PRG4 mRNA levels resulted strongly correlated with increased survival rate of HCC patients (p = 0.000) in a prospective study involving 78 HCC subjects. We next showed that transforming growth factor beta stimulates PRG4 expression and secretion by primary human HCC cancer-associated fibroblasts, non-invasive HCC cell lines, and ex vivo specimens. By functional tests we found that recombinant human PRG4 (rhPRG4) impairs HCC cell migration. More importantly, the treatment of HCC cells expressing CD44 (the main PRG4 receptor) with rhPRG4 dramatically enhances the growth-limiting capacity of sorafenib and regorafenib, whereas not significantly affecting cell proliferation per se. Conversely, rhPRG4 only poorly potentiates drug effectiveness on low CD44-expressing or stably CD44-silenced HCC cells. Overall, these data suggest that the physiologically-produced compound PRG4 may function as a novel tumor-suppressive agent by strengthening sorafenib and regorafenib effects in the treatment of HCC.
Sorafenib and regorafenib administration is among the preferential approaches to treat hepatocellular carcinoma (HCC), but does not provide satisfactory benefits. Intensive crosstalk occurring between cancer cells and other multiple non-cancerous cell subsets present in the surrounding microenvironment is assumed to affect tumor progression. This interplay is mediated by a number of soluble and structural extracellular matrix (ECM) proteins enriching the stromal milieu. Here we assess the HCC tumor expression of the ECM protein proteoglycan 4 (PRG4) and its potential pharmacologic activity either alone, or in combination with sorafenib and regorafenib. PRG4 mRNA levels resulted strongly correlated with increased survival rate of HCC patients ( p  = 0.000) in a prospective study involving 78 HCC subjects. We next showed that transforming growth factor beta stimulates PRG4 expression and secretion by primary human HCC cancer-associated fibroblasts, non-invasive HCC cell lines, and ex vivo specimens. By functional tests we found that recombinant human PRG4 (rhPRG4) impairs HCC cell migration. More importantly, the treatment of HCC cells expressing CD44 (the main PRG4 receptor) with rhPRG4 dramatically enhances the growth-limiting capacity of sorafenib and regorafenib, whereas not significantly affecting cell proliferation per se. Conversely, rhPRG4 only poorly potentiates drug effectiveness on low CD44-expressing or stably CD44-silenced HCC cells. Overall, these data suggest that the physiologically-produced compound PRG4 may function as a novel tumor-suppressive agent by strengthening sorafenib and regorafenib effects in the treatment of HCC.
Sorafenib and regorafenib administration is among the preferential approaches to treat hepatocellular carcinoma (HCC), but does not provide satisfactory benefits. Intensive crosstalk occurring between cancer cells and other multiple non-cancerous cell subsets present in the surrounding microenvironment is assumed to affect tumor progression. This interplay is mediated by a number of soluble and structural extracellular matrix (ECM) proteins enriching the stromal milieu. Here we assess the HCC tumor expression of the ECM protein proteoglycan 4 (PRG4) and its potential pharmacologic activity either alone, or in combination with sorafenib and regorafenib. PRG4 mRNA levels resulted strongly correlated with increased survival rate of HCC patients (p = 0.000) in a prospective study involving 78 HCC subjects. We next showed that transforming growth factor beta stimulates PRG4 expression and secretion by primary human HCC cancer-associated fibroblasts, non-invasive HCC cell lines, and ex vivo specimens. By functional tests we found that recombinant human PRG4 (rhPRG4) impairs HCC cell migration. More importantly, the treatment of HCC cells expressing CD44 (the main PRG4 receptor) with rhPRG4 dramatically enhances the growth-limiting capacity of sorafenib and regorafenib, whereas not significantly affecting cell proliferation per se. Conversely, rhPRG4 only poorly potentiates drug effectiveness on low CD44-expressing or stably CD44-silenced HCC cells. Overall, these data suggest that the physiologically-produced compound PRG4 may function as a novel tumor-suppressive agent by strengthening sorafenib and regorafenib effects in the treatment of HCC.
ArticleNumber 984
Author Scialpi, Rosanna
Schmidt, Tannin A.
Giannelli, Gianluigi
Mancarella, Serena
Dituri, Francesco
Frusciante, Martina
Villa, Erica
Lupo, Luigi Giovanni
Author_xml – sequence: 1
  givenname: Francesco
  surname: Dituri
  fullname: Dituri, Francesco
  email: francesco.dituri@irccsdebellis.it
  organization: National Institute of Gastroenterology “S. De Bellis” Research Hospital
– sequence: 2
  givenname: Rosanna
  surname: Scialpi
  fullname: Scialpi, Rosanna
  organization: National Institute of Gastroenterology “S. De Bellis” Research Hospital
– sequence: 3
  givenname: Tannin A.
  surname: Schmidt
  fullname: Schmidt, Tannin A.
  organization: Biomedical Engineering Department, University of Connecticut Health Centre
– sequence: 4
  givenname: Martina
  surname: Frusciante
  fullname: Frusciante, Martina
  organization: National Institute of Gastroenterology “S. De Bellis” Research Hospital
– sequence: 5
  givenname: Serena
  surname: Mancarella
  fullname: Mancarella, Serena
  organization: National Institute of Gastroenterology “S. De Bellis” Research Hospital
– sequence: 6
  givenname: Luigi Giovanni
  surname: Lupo
  fullname: Lupo, Luigi Giovanni
  organization: University of Bari, Department of General Surgery and Liver Transplantation, Policlinico - piazza Giulio Cesare 14
– sequence: 7
  givenname: Erica
  orcidid: 0000-0001-6388-7022
  surname: Villa
  fullname: Villa, Erica
  organization: Gastroenterology Unit, Department of Internal Medicine, University of Modena and Reggio Emilia
– sequence: 8
  givenname: Gianluigi
  surname: Giannelli
  fullname: Giannelli, Gianluigi
  organization: National Institute of Gastroenterology “S. De Bellis” Research Hospital
BackLink https://www.ncbi.nlm.nih.gov/pubmed/33199679$$D View this record in MEDLINE/PubMed
BookMark eNp9Us1uFSEYJabG1toXcGFI3LgZhYFhYGNixp-aNNGFrgnDfHMvzVy4AjOmb-Bjy_S2tXZRWPB3zuF8cJ6jIx88IPSSkreUMPkuccqpqkhNKsKoJJV8gk5qwmnFpVRH9-bH6CylS1IaY6RuxDN0zBhVSrTqBP35HkOGsJmurPEVxy5hG2KEyWQY8G-Xt3gKfgMRpzkubjETdh6fdx3em-zA54SNHzD4rfEWEk4hmhG866-3I2zu1jCOYLNbwENKeHEGdx85X9UWl2N4gZ6OZkpwdjOeop-fP_3ozquLb1--dh8uKstbnque9-3AWjFKKcZBECJkM9ZSNpYLU9OGNKLUzS2HQXBoe8nYWDojVFkp5cBO0fuD7n7udzDYUkI0k95HtzPxSgfj9P8n3m31Jiy6FUKVS4vAmxuBGH7NkLLeuWRhmoyHMCddc0GZUlTJAn39AHoZ5uhLeQXV0ka0VPGCenXf0Z2V208qAHkA2BhSijBq63J5_bAadJOmRK-R0IdI6BIJfR0JvTqoH1Bv1R8lsQMpFfD69_9sP8L6C0wIySU
CitedBy_id crossref_primary_10_1016_j_bbrc_2021_01_017
crossref_primary_10_1016_j_celrep_2024_113877
crossref_primary_10_3389_fimmu_2022_951459
crossref_primary_10_1016_j_compbiomed_2024_108541
crossref_primary_10_3390_cancers13061261
crossref_primary_10_3892_ijo_2022_5335
crossref_primary_10_1186_s12951_025_03214_3
crossref_primary_10_1016_j_jare_2024_04_007
crossref_primary_10_1186_s13046_024_03210_9
crossref_primary_10_2147_PGPM_S349350
crossref_primary_10_1002_ctm2_536
crossref_primary_10_1186_s13046_022_02536_6
crossref_primary_10_3390_cancers15020373
crossref_primary_10_3390_cancers14081902
crossref_primary_10_1016_j_tice_2024_102409
crossref_primary_10_3389_fonc_2022_1023801
crossref_primary_10_3389_fonc_2022_883831
crossref_primary_10_3390_ijms26062430
crossref_primary_10_3389_fmolb_2023_1162409
Cites_doi 10.1002/jor.23247
10.1002/hep.22283
10.1002/art.22974
10.1089/ten.tea.2014.0381
10.1016/j.tripleo.2011.07.001
10.1016/j.canlet.2008.12.031
10.1002/art.39030
10.1002/hep.23118
10.1186/s13075-015-0877-x
10.1016/j.jhep.2017.08.013
10.1126/scitranslmed.3005409
10.1172/JCI200522263
10.1080/15216540500531713
10.1016/j.atherosclerosis.2018.06.883
10.1371/journal.pone.0210601
10.1186/s12891-015-0842-5
10.1002/hep.22731
10.1002/hep.22201
10.1002/pros.20182
10.1038/srep18910
10.3109/03008209209014228
10.1002/jcb.20189
10.1016/S0140-6736(18)30207-1
10.1006/abbi.1994.1219
10.1002/hep.21936
10.1016/j.bbadis.2018.11.009
10.1038/15496
10.1158/1078-0432.CCR-14-2602
10.3390/cancers11070985
10.1136/gutjnl-2014-307323
10.1002/art.34674
10.1016/S0140-6736(16)32453-9
10.1056/NEJMoa1717002
10.1002/art.39087
10.3748/wjg.v20.i15.4128
10.1002/ijc.29097
10.1002/(SICI)1097-4636(19980605)40:3<414::AID-JBM11>3.0.CO;2-J
10.1016/j.biopha.2019.109032
10.1016/j.canlet.2017.01.037
10.1111/febs.13665
10.1007/978-3-030-21540-8_14
10.1016/j.ccell.2018.05.003
10.1016/j.semcancer.2019.07.026
10.1038/s41419-018-0384-5
10.1053/j.gastro.2017.09.007
10.3389/fcell.2017.00018
10.1038/cddis.2017.469
10.1371/journal.pone.0219697
10.1186/s13075-017-1301-5
10.1074/jbc.M116.752451
10.2174/1389203718666171117112619
10.18632/oncotarget.14523
10.1136/gutjnl-2014-308483
10.1002/hep.24485
10.1007/s00280-010-1459-x
10.1042/BSR20171264
10.1111/liv.14113
10.1158/0008-5472.CAN-18-2019
10.1172/JCI200524282C1
10.1002/hep.23285
ContentType Journal Article
Copyright The Author(s) 2020
The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
Copyright_xml – notice: The Author(s) 2020
– notice: The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
DBID C6C
AAYXX
CITATION
CGR
CUY
CVF
ECM
EIF
NPM
3V.
7X7
7XB
88A
88I
8FE
8FH
8FI
8FJ
8FK
ABUWG
AFKRA
AZQEC
BBNVY
BENPR
BHPHI
CCPQU
DWQXO
FYUFA
GHDGH
GNUQQ
HCIFZ
K9.
LK8
M0S
M2P
M7P
PHGZM
PHGZT
PIMPY
PKEHL
PQEST
PQGLB
PQQKQ
PQUKI
PRINS
Q9U
7X8
5PM
DOI 10.1038/s41419-020-03180-8
DatabaseName Springer Nature OA Free Journals
CrossRef
Medline
MEDLINE
MEDLINE (Ovid)
MEDLINE
MEDLINE
PubMed
ProQuest Central (Corporate)
Health & Medical Collection (ProQuest)
ProQuest Central (purchase pre-March 2016)
Biology Database (Alumni Edition)
Science Database (Alumni Edition)
ProQuest SciTech Collection
ProQuest Natural Science Journals
Hospital Premium Collection
Hospital Premium Collection (Alumni Edition)
ProQuest Central (Alumni) (purchase pre-March 2016)
ProQuest Central (Alumni)
ProQuest Central UK/Ireland
ProQuest Central Essentials
Biological Science Collection
ProQuest Central
Natural Science Collection
ProQuest One
ProQuest Central Korea
Health Research Premium Collection
Health Research Premium Collection (Alumni)
ProQuest Central Student
SciTech Premium Collection
ProQuest Health & Medical Complete (Alumni)
Biological Sciences
ProQuest Health & Medical Collection
Science Database (ProQuest)
Biological Science Database
ProQuest Central Premium
ProQuest One Academic (New)
Publicly Available Content Database
ProQuest One Academic Middle East (New)
ProQuest One Academic Eastern Edition (DO NOT USE)
ProQuest One Applied & Life Sciences
ProQuest One Academic
ProQuest One Academic UKI Edition
ProQuest Central China
ProQuest Central Basic
MEDLINE - Academic
PubMed Central (Full Participant titles)
DatabaseTitle CrossRef
MEDLINE
Medline Complete
MEDLINE with Full Text
PubMed
MEDLINE (Ovid)
Publicly Available Content Database
ProQuest Central Student
ProQuest One Academic Middle East (New)
ProQuest Central Essentials
ProQuest Health & Medical Complete (Alumni)
ProQuest Central (Alumni Edition)
SciTech Premium Collection
ProQuest One Community College
ProQuest Natural Science Collection
ProQuest Central China
ProQuest Biology Journals (Alumni Edition)
ProQuest Central
ProQuest One Applied & Life Sciences
Health Research Premium Collection
Health and Medicine Complete (Alumni Edition)
Natural Science Collection
ProQuest Central Korea
Biological Science Collection
ProQuest Central (New)
ProQuest Science Journals (Alumni Edition)
ProQuest Biological Science Collection
ProQuest Central Basic
ProQuest Science Journals
ProQuest One Academic Eastern Edition
ProQuest Hospital Collection
Health Research Premium Collection (Alumni)
Biological Science Database
ProQuest SciTech Collection
ProQuest Hospital Collection (Alumni)
ProQuest Health & Medical Complete
ProQuest One Academic UKI Edition
ProQuest One Academic
ProQuest One Academic (New)
ProQuest Central (Alumni)
MEDLINE - Academic
DatabaseTitleList MEDLINE - Academic
CrossRef


MEDLINE
Publicly Available Content Database
Database_xml – sequence: 1
  dbid: C6C
  name: Springer Nature Link
  url: http://www.springeropen.com/
  sourceTypes: Publisher
– sequence: 2
  dbid: NPM
  name: PubMed
  url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
  sourceTypes: Index Database
– sequence: 3
  dbid: EIF
  name: MEDLINE
  url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search
  sourceTypes: Index Database
– sequence: 4
  dbid: BENPR
  name: ProQuest Central
  url: http://www.proquest.com/pqcentral?accountid=15518
  sourceTypes: Aggregation Database
DeliveryMethod fulltext_linktorsrc
Discipline Biology
EISSN 2041-4889
ExternalDocumentID PMC7669886
33199679
10_1038_s41419_020_03180_8
Genre Research Support, Non-U.S. Gov't
Journal Article
GrantInformation_xml – fundername: Associazione Italiana per la Ricerca sul Cancro (Italian Association for Cancer Research)
  grantid: 18737
  funderid: https://doi.org/10.13039/501100005010
– fundername: Ministero della Salute (Ministry of Health, Italy)
  grantid: 5 x 1000 2017-2019
  funderid: https://doi.org/10.13039/501100003196
– fundername: ;
  grantid: 5 x 1000 2017-2019
– fundername: ;
  grantid: 18737
GroupedDBID ---
0R~
3V.
53G
5VS
70F
7X7
88A
88I
8FE
8FH
8FI
8FJ
AAJSJ
ABUWG
ACGFS
ACSMW
ADBBV
AENEX
AFKRA
AJTQC
ALIPV
ALMA_UNASSIGNED_HOLDINGS
AOIJS
AZQEC
BAWUL
BBNVY
BCNDV
BENPR
BHPHI
BPHCQ
BVXVI
C6C
CCPQU
DIK
DWQXO
E3Z
EBLON
EBS
EMOBN
FRP
FYUFA
GNUQQ
GROUPED_DOAJ
HCIFZ
HMCUK
HYE
HZ~
KQ8
LK8
M0L
M2P
M48
M7P
M~E
NAO
O5R
O5S
O9-
OK1
PIMPY
PQQKQ
PROAC
RNT
RPM
SNYQT
TR2
UKHRP
W2D
AASML
AAYXX
CITATION
PHGZM
PHGZT
CGR
CUY
CVF
ECM
EIF
NPM
7XB
8FK
AARCD
K9.
PKEHL
PQEST
PQGLB
PQUKI
PRINS
Q9U
7X8
PUEGO
5PM
ID FETCH-LOGICAL-c474t-b4b7d376f886fd600685f2885c46a2150560414c4ed64e7b833f3f33019c888d3
IEDL.DBID M48
ISSN 2041-4889
IngestDate Thu Aug 21 18:31:34 EDT 2025
Thu Sep 04 19:09:36 EDT 2025
Wed Aug 13 02:41:38 EDT 2025
Mon Jul 21 05:59:29 EDT 2025
Thu Apr 24 23:09:24 EDT 2025
Tue Jul 01 03:49:50 EDT 2025
Fri Feb 21 02:36:54 EST 2025
IsDoiOpenAccess true
IsOpenAccess true
IsPeerReviewed true
IsScholarly true
Issue 11
Language English
License Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
LinkModel DirectLink
MergedId FETCHMERGED-LOGICAL-c474t-b4b7d376f886fd600685f2885c46a2150560414c4ed64e7b833f3f33019c888d3
Notes ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
content type line 23
ORCID 0000-0001-6388-7022
OpenAccessLink https://www.proquest.com/docview/2471567194?pq-origsite=%requestingapplication%
PMID 33199679
PQID 2471567194
PQPubID 2041963
ParticipantIDs pubmedcentral_primary_oai_pubmedcentral_nih_gov_7669886
proquest_miscellaneous_2461399198
proquest_journals_2471567194
pubmed_primary_33199679
crossref_citationtrail_10_1038_s41419_020_03180_8
crossref_primary_10_1038_s41419_020_03180_8
springer_journals_10_1038_s41419_020_03180_8
ProviderPackageCode CITATION
AAYXX
PublicationCentury 2000
PublicationDate 2020-11-16
PublicationDateYYYYMMDD 2020-11-16
PublicationDate_xml – month: 11
  year: 2020
  text: 2020-11-16
  day: 16
PublicationDecade 2020
PublicationPlace London
PublicationPlace_xml – name: London
– name: England
PublicationTitle Cell death & disease
PublicationTitleAbbrev Cell Death Dis
PublicationTitleAlternate Cell Death Dis
PublicationYear 2020
Publisher Nature Publishing Group UK
Springer Nature B.V
Publisher_xml – name: Nature Publishing Group UK
– name: Springer Nature B.V
References Torrecilla (CR6) 2017; 67
Jay, Haberstroh, Cha (CR28) 1998; 40
Fernando (CR27) 2015; 136
Alquraini (CR39) 2015; 17
Mazzocca, Fransvea, Lavezzari, Antonaci, Giannelli (CR19) 2009; 50
Waller, Zhang, Jay (CR44) 2016; 34
Mazzocca (CR11) 2010; 51
Malfettone (CR26) 2017; 392
Mazzocca (CR10) 2011; 54
Giannelli, Rani, Dituri, Cao, Palasciano (CR9) 2014; 63
Sarkar (CR23) 2019; 14
Rani (CR8) 2014; 20
Roedig (CR13) 2020; 62
Senbanjo, Chellaiah (CR24) 2017; 5
Schumacher, Block, Schmid, Aydelotte, Kuettner (CR32) 1994; 311
Iqbal (CR38) 2016; 6
Rhee (CR45) 2005; 115
Alquraini (CR58) 2017; 19
Nahon (CR49) 2019; 1865
CR7
Kudo (CR1) 2018; 391
Weng (CR61) 2018; 38
Cuellar, Reddi (CR41) 2015; 21
Jay (CR43) 2007; 56
Fabregat (CR53) 2016; 283
Xu, Wu, Feng, Lin, Gu (CR40) 2012; 114
Nault, Villanueva (CR5) 2015; 21
Bataller, Brenner (CR12) 2005; 115
Bruix (CR2) 2017; 389
Chen (CR57) 2018; 154
Al-Sharif (CR42) 2015; 67
Fransvea (CR20) 2011; 68
Heegaard, Xie, Young, Nielsen (CR16) 2004; 93
Dhar (CR25) 2018; 33
Jay, Britt, Cha (CR29) 2000; 27
Ludwig, Hunter, Schmidt (CR31) 2015; 16
Marcelino (CR47) 1999; 23
Rani (CR22) 2018; 9
Weng (CR60) 2019; 116
Yeh, Lee, Chang, Lang, Jou (CR51) 2019; 79
Chavez, Sohn, Serra (CR34) 2019; 14
Fransvea, Angelotti, Antonaci, Giannelli (CR17) 2008; 47
Cross (CR15) 2005; 63
Abou-Alfa (CR3) 2018; 379
Kok (CR4) 2019; 11
Nikitovic (CR14) 2006; 58
Jay (CR30) 1992; 28
Moreno-Càceres (CR52) 2017; 8
Villa (CR50) 2016; 65
Ghatak (CR55) 2017; 292
Nahon, Hoekstra, Van Eck (CR46) 2018; 278
Kozhemyakina (CR48) 2015; 67
Zhang (CR56) 2017; 8
Fransvea, Mazzocca, Antonaci, Giannelli (CR18) 2009; 49
Ludwig, McAllister, Lun, Wiley, Schmidt (CR33) 2012; 64
Bergamini (CR36) 2007; 46
Faivre (CR21) 2019; 39
Ruan (CR35) 2013; 5
Coulouarn, Factor, Thorgeirsson (CR37) 2008; 47
Wu (CR59) 2009; 278
Arrese (CR54) 2017; 19
S Faivre (3180_CR21) 2019; 39
B Rani (3180_CR22) 2018; 9
E Kozhemyakina (3180_CR48) 2015; 67
GK Abou-Alfa (3180_CR3) 2018; 379
TE Ludwig (3180_CR33) 2012; 64
J Chen (3180_CR57) 2018; 154
M Kudo (3180_CR1) 2018; 391
AM Heegaard (3180_CR16) 2004; 93
M Arrese (3180_CR54) 2017; 19
TE Ludwig (3180_CR31) 2015; 16
H Roedig (3180_CR13) 2020; 62
JM Wu (3180_CR59) 2009; 278
C Bergamini (3180_CR36) 2007; 46
V Kok (3180_CR4) 2019; 11
R Bataller (3180_CR12) 2005; 115
GD Jay (3180_CR29) 2000; 27
HW Yeh (3180_CR51) 2019; 79
J Moreno-Càceres (3180_CR52) 2017; 8
A Alquraini (3180_CR58) 2017; 19
MC Weng (3180_CR61) 2018; 38
RD Chavez (3180_CR34) 2019; 14
G Giannelli (3180_CR9) 2014; 63
E Fransvea (3180_CR18) 2009; 49
MC Weng (3180_CR60) 2019; 116
A Malfettone (3180_CR26) 2017; 392
GD Jay (3180_CR30) 1992; 28
A Al-Sharif (3180_CR42) 2015; 67
KA Waller (3180_CR44) 2016; 34
DK Rhee (3180_CR45) 2005; 115
GD Jay (3180_CR43) 2007; 56
I Fabregat (3180_CR53) 2016; 283
E Villa (3180_CR50) 2016; 65
X Zhang (3180_CR56) 2017; 8
A Sarkar (3180_CR23) 2019; 14
A Cuellar (3180_CR41) 2015; 21
S Torrecilla (3180_CR6) 2017; 67
E Fransvea (3180_CR20) 2011; 68
C Coulouarn (3180_CR37) 2008; 47
D Dhar (3180_CR25) 2018; 33
A Alquraini (3180_CR39) 2015; 17
J Bruix (3180_CR2) 2017; 389
JC Nault (3180_CR5) 2015; 21
J Marcelino (3180_CR47) 1999; 23
S Ghatak (3180_CR55) 2017; 292
T Xu (3180_CR40) 2012; 114
JE Nahon (3180_CR49) 2019; 1865
A Mazzocca (3180_CR19) 2009; 50
JE Nahon (3180_CR46) 2018; 278
J Fernando (3180_CR27) 2015; 136
A Mazzocca (3180_CR10) 2011; 54
LT Senbanjo (3180_CR24) 2017; 5
E Fransvea (3180_CR17) 2008; 47
D Nikitovic (3180_CR14) 2006; 58
B Rani (3180_CR8) 2014; 20
GD Jay (3180_CR28) 1998; 40
3180_CR7
NA Cross (3180_CR15) 2005; 63
BL Schumacher (3180_CR32) 1994; 311
A Mazzocca (3180_CR11) 2010; 51
SM Iqbal (3180_CR38) 2016; 6
MZC Ruan (3180_CR35) 2013; 5
References_xml – volume: 51
  start-page: 523
  year: 2010
  end-page: 534
  ident: CR11
  article-title: Down-regulation of connective tissue growth factor by inhibition of transforming growth factor β blocks the tumor-stroma cross-talk and tumor progression in hepatocellular carcinoma
  publication-title: Hepatology
– volume: 33
  start-page: 1061
  year: 2018
  end-page: 1077
  ident: CR25
  article-title: Liver cancer initiation requires p53 inhibition by CD44-enhanced growth factor signaling
  publication-title: Cancer Cell
– volume: 34
  start-page: S1
  year: 2016
  ident: CR44
  article-title: Friction-induced inflammation influences joint deterioration in Prg4 knockout mice.
  publication-title: J. Orthop. Res.
  doi: 10.1002/jor.23247
– volume: 47
  start-page: 2059
  year: 2008
  end-page: 2067
  ident: CR37
  article-title: Transforming growth factor-β gene expression signature in mouse hepatocytes predicts clinical outcome in human cancer
  publication-title: Hepatology
  doi: 10.1002/hep.22283
– volume: 136
  start-page: E161
  year: 2015
  end-page: E172
  ident: CR27
  article-title: A mesenchymal-like phenotype and expression of CD44 predict lack of apoptotic response to sorafenib in liver tumor cells
  publication-title: Int. J. Cancer
– volume: 40
  start-page: 414
  year: 1998
  end-page: 418
  ident: CR28
  article-title: Comparison of the boundary-lubricating ability of bovine synovial fluid, lubricin, and Healon
  publication-title: J. Biomed. Mater. Res.
– volume: 56
  start-page: 3662
  year: 2007
  end-page: 3669
  ident: CR43
  article-title: Association between friction and wear in diarthrodial joints lacking lubricin
  publication-title: Arthritis Rheum.
  doi: 10.1002/art.22974
– volume: 283
  start-page: 2219
  year: 2016
  end-page: 2232
  ident: CR53
  article-title: TGF-β signalling and liver disease
  publication-title: FEBS J.
– volume: 21
  start-page: 1973
  year: 2015
  end-page: 1981
  ident: CR41
  article-title: Stimulation of superficial zone protein/lubricin/PRG4 by transforming growth factor-β in superficial zone articular chondrocytes and modulation by glycosaminoglycans
  publication-title: Tissue Eng. Part A
  doi: 10.1089/ten.tea.2014.0381
– volume: 114
  start-page: 183
  year: 2012
  end-page: 192
  ident: CR40
  article-title: Combination of intermittent hydrostatic pressure linking TGF-β1, TNF-α on modulation of proteoglycan 4 metabolism in rat temporomandibular synovial fibroblasts
  publication-title: Oral. Surg. Oral. Med. Oral. Pathol. Oral. Radiol.
  doi: 10.1016/j.tripleo.2011.07.001
– volume: 19
  start-page: 1172
  year: 2017
  end-page: 1179
  ident: CR54
  article-title: TGF-β and hepatocellular carcinoma: when a friend becomes an enemy
  publication-title: Curr. Protein Pept. Sci.
– volume: 115
  start-page: 1100
  year: 2005
  ident: CR12
  article-title: Liver fibrosis
  publication-title: J. Clin. Invest.
– volume: 5
  start-page: 18
  year: 2017
  ident: CR24
  article-title: CD44: A multifunctional cell surface adhesion receptor is a regulator of progression and metastasis of cancer cells
  publication-title: Front. Cell Dev. Biol.
– volume: 38
  start-page: BSR20171264
  year: 2018
  ident: CR61
  article-title: Regorafenib inhibits tumor progression through suppression of ERK/NF-κB activation in hepatocellular carcinoma bearing mice
  publication-title: Biosci. Rep.
– volume: 278
  start-page: 145
  year: 2009
  end-page: 155
  ident: CR59
  article-title: NF-κB inhibition in human hepatocellular carcinoma and its potential as adjunct to sorafenib based therapy
  publication-title: Cancer Lett.
  doi: 10.1016/j.canlet.2008.12.031
– volume: 9
  year: 2018
  ident: CR22
  article-title: Galunisertib suppresses the staminal phenotype in hepatocellular carcinoma by modulating CD44 expression
  publication-title: Cell Death Dis.
– volume: 67
  start-page: 1261
  year: 2015
  end-page: 1273
  ident: CR48
  article-title: Identification of a Prg4-expressing articular cartilage progenitor cell population in mice
  publication-title: Arthritis Rheumatol.
  doi: 10.1002/art.39030
– volume: 50
  start-page: 1140
  year: 2009
  end-page: 1151
  ident: CR19
  article-title: Inhibition of transforming growth factor β receptor I kinase blocks hepatocellular carcinoma growth through neo-angiogenesis regulation
  publication-title: Hepatology
  doi: 10.1002/hep.23118
– volume: 62
  start-page: 31
  year: 2020
  end-page: 47
  ident: CR13
  article-title: Danger matrix molecules orchestrate CD14/CD44 signaling in cancer development
  publication-title: Semin. Cancer Biol.
– volume: 17
  start-page: 353
  year: 2015
  ident: CR39
  article-title: The interaction of lubricin/proteoglycan 4 (PRG4) with toll-like receptors 2 and 4: An anti-inflammatory role of PRG4 in synovial fluid
  publication-title: Arthritis Res. Ther.
  doi: 10.1186/s13075-015-0877-x
– volume: 67
  start-page: 1222
  year: 2017
  end-page: 1231
  ident: CR6
  article-title: Trunk mutational events present minimal intra- and inter-tumoral heterogeneity in hepatocellular carcinoma
  publication-title: J. Hepatol.
  doi: 10.1016/j.jhep.2017.08.013
– volume: 5
  start-page: 176ra34
  year: 2013
  ident: CR35
  article-title: Proteoglycan 4 expression protects against the development of osteoarthritis
  publication-title: Sci. Transl. Med.
  doi: 10.1126/scitranslmed.3005409
– volume: 8
  year: 2017
  ident: CR52
  article-title: The level of caveolin-1 expression determines response to TGF-β as a tumour suppressor in hepatocellular carcinoma cells
  publication-title: Cell Death Dis.
– volume: 115
  start-page: 622
  year: 2005
  end-page: 631
  ident: CR45
  article-title: The secreted glycoprotein lubricin protects cartilage surfaces and inhibits synovial cell overgrowth
  publication-title: J. Clin. Invest.
  doi: 10.1172/JCI200522263
– volume: 292
  start-page: 10465
  year: 2017
  end-page: 10489
  ident: CR55
  article-title: Transforming growth factor β1 (TGF β1) regulates CD44V6 expression and activity through extracellular signal-regulated kinase (ERK)-induced EGR1 in pulmonary fibrogenic fibroblasts
  publication-title: J. Biol. Chem.
– volume: 58
  start-page: 47
  year: 2006
  end-page: 53
  ident: CR14
  article-title: Transforming growth factor-β as a key molecule triggering the expression of versican isoforms V0 and V1, hyaluronan synthase-2 and synthesis of hyaluronan in malignant osteosarcoma cells
  publication-title: IUBMB Life
  doi: 10.1080/15216540500531713
– volume: 27
  start-page: 594
  year: 2000
  end-page: 600
  ident: CR29
  article-title: Lubricin is a product of megakaryocyte stimulating factor gene expression by human synovial fibroblasts
  publication-title: J. Rheumatol.
– volume: 39
  start-page: 1468
  year: 2019
  end-page: 1477
  ident: CR21
  article-title: Novel transforming growth factor beta receptor I kinase inhibitor galunisertib (LY2157299) in advanced hepatocellular carcinoma
  publication-title: Liver Int.
– volume: 278
  start-page: 315
  year: 2018
  end-page: 316
  ident: CR46
  article-title: Total body proteoglycan 4 (Prg4) deficiency increases atherosclerosis susceptibility in apolipoprotein E knockout and low-density lipoprotein receptor knockout mice
  publication-title: Atherosclerosis
  doi: 10.1016/j.atherosclerosis.2018.06.883
– volume: 14
  start-page: e0210601
  year: 2019
  ident: CR34
  article-title: Prg4 prevents osteoarthritis induced by dominant-negative interference of TGF-β signaling in mice
  publication-title: PLoS ONE
  doi: 10.1371/journal.pone.0210601
– volume: 19
  start-page: 89
  year: 2017
  ident: CR58
  article-title: The autocrine role of proteoglycan-4 (PRG4) in modulating osteoarthritic synoviocyte proliferation and expression of matrix degrading enzymes
  publication-title: Arthritis Res. Ther.
– volume: 392
  start-page: 39
  year: 2017
  end-page: 50
  ident: CR26
  article-title: Transforming growth factor-β-induced plasticity causes a migratory stemness phenotype in hepatocellular carcinoma
  publication-title: Cancer Lett.
– volume: 16
  year: 2015
  ident: CR31
  article-title: Cartilage boundary lubrication synergism is mediated by hyaluronan concentration and PRG4 concentration and structure
  publication-title: BMC Musculoskelet. Disord.
  doi: 10.1186/s12891-015-0842-5
– volume: 65
  start-page: 861
  year: 2016
  end-page: 869
  ident: CR50
  article-title: Neoangiogenesis-related genes are hallmarks of fast-growing hepatocellular carcinomas and worst survival. results from a prospective study
  publication-title: Gut
– volume: 49
  start-page: 839
  year: 2009
  end-page: 850
  ident: CR18
  article-title: Targeting transforming growth factor (TGF)-βRI inhibits activation of β1 integrin and blocks vascular invasion in hepatocellular carcinoma
  publication-title: Hepatology
  doi: 10.1002/hep.22731
– volume: 47
  start-page: 1557
  year: 2008
  end-page: 1566
  ident: CR17
  article-title: Blocking transforming growth factor-beta up-regulates E-cadherin and reduces migration and invasion of hepatocellular carcinoma cells
  publication-title: Hepatology
  doi: 10.1002/hep.22201
– volume: 63
  start-page: 269
  year: 2005
  end-page: 275
  ident: CR15
  article-title: The expression and regulation of ADAMTS-1, -4, -5, -9, and -15, and TIMP-3 by TGFβ1 in prostate cells: relevance to the accumulation of versican
  publication-title: Prostate
  doi: 10.1002/pros.20182
– volume: 6
  year: 2016
  ident: CR38
  article-title: Lubricin/proteoglycan 4 binds to and regulates the activity of toll-like receptors in vitro
  publication-title: Sci. Rep.
  doi: 10.1038/srep18910
– volume: 116
  start-page: 109032
  year: 2019
  ident: CR60
  article-title: Apoptosis induction and AKT/NF-κB inactivation are associated with regroafenib-inhibited tumor progression in non-small cell lung cancer in vitro and in vivo
  publication-title: Biomed. Pharmacother.
– volume: 28
  start-page: 71
  year: 1992
  end-page: 88
  ident: CR30
  article-title: Characterization of a bovine synovial fluid lubricating factor. I. Chemical, surface activity and lubricating properties
  publication-title: Connect. Tissue Res.
  doi: 10.3109/03008209209014228
– volume: 93
  start-page: 463
  year: 2004
  end-page: 475
  ident: CR16
  article-title: Transforming growth factor beta stimulation of biglycan gene expression is potentially mediated by Sp1 binding factors
  publication-title: J. Cell Biochem.
  doi: 10.1002/jcb.20189
– volume: 391
  start-page: 1163
  year: 2018
  end-page: 1173
  ident: CR1
  article-title: Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial
  publication-title: Lancet
  doi: 10.1016/S0140-6736(18)30207-1
– volume: 14
  start-page: e0219697
  year: 2019
  ident: CR23
  article-title: Recombinant human PRG4 (rhPRG4) suppresses breast cancer cell invasion by inhibiting TGFβ-Hyaluronan-CD44 signalling pathway
  publication-title: PLoS ONE
– volume: 311
  start-page: 144
  year: 1994
  end-page: 152
  ident: CR32
  article-title: A novel proteoglycan synthesized and secreted by chondrocytes of the superficial zone of articular cartilage
  publication-title: Arch. Biochem. Biophys.
  doi: 10.1006/abbi.1994.1219
– volume: 79
  start-page: 3797
  year: 2019
  end-page: 3805
  ident: CR51
  article-title: A new switch for TGFβ in cancer
  publication-title: Cancer Res.
– volume: 46
  start-page: 1801
  year: 2007
  end-page: 1809
  ident: CR36
  article-title: Laminin-5 stimulates hepatocellular carcinoma growth through a different function of α6β4 and α3β1 integrins
  publication-title: Hepatology
  doi: 10.1002/hep.21936
– volume: 1865
  start-page: 494
  year: 2019
  end-page: 501
  ident: CR49
  article-title: Proteoglycan 4 deficiency protects against glucose intolerance and fatty liver disease in diet-induced obese mice
  publication-title: Biochim. Biophys. Acta - Mol. Basis Dis.
  doi: 10.1016/j.bbadis.2018.11.009
– volume: 23
  start-page: 319
  year: 1999
  end-page: 322
  ident: CR47
  article-title: CACP, encoding a secreted proteoglycan, is mutated in camptodactyly-arthropathy-coxa vara-pericarditis syndrome
  publication-title: Nat. Genet.
  doi: 10.1038/15496
– volume: 8
  start-page: 29785
  year: 2017
  end-page: 29794
  ident: CR56
  article-title: Transforming growth factor-beta1 suppresses hepatocellular carcinoma proliferation via activation of Hippo signaling
  publication-title: Oncotarget
– volume: 21
  start-page: 1786
  year: 2015
  end-page: 1788
  ident: CR5
  article-title: Intratumor Molecular and phenotypic diversity in hepatocellular carcinoma
  publication-title: Clin. Cancer Res.
  doi: 10.1158/1078-0432.CCR-14-2602
– volume: 11
  start-page: 985
  year: 2019
  ident: CR4
  article-title: Sorafenib with transarterial chemoembolization achieves improved survival vs. sorafenib alone in advanced hepatocellular carcinoma: A nationwide population-based cohort study
  publication-title: Cancers (Basel)
  doi: 10.3390/cancers11070985
– volume: 63
  start-page: 1668
  year: 2014
  end-page: 1676
  ident: CR9
  article-title: Moving towards personalised therapy in patients with hepatocellular carcinoma: The role of the microenvironment
  publication-title: Gut
  doi: 10.1136/gutjnl-2014-307323
– volume: 64
  start-page: 3963
  year: 2012
  end-page: 3971
  ident: CR33
  article-title: Diminished cartilage-lubricating ability of human osteoarthritic synovial fluid deficient in proteoglycan 4: Restoration through proteoglycan 4 supplementation
  publication-title: Arthritis Rheum.
  doi: 10.1002/art.34674
– volume: 54
  start-page: 920
  year: 2011
  end-page: 930
  ident: CR10
  article-title: Tumor-secreted lysophostatidic acid accelerates hepatocellular carcinoma progression by promoting differentiation of peritumoral fibroblasts in myofibroblasts
  publication-title: Hepatology
– volume: 154
  start-page: 195
  year: 2018
  end-page: 210
  ident: CR57
  article-title: Analysis of genomes and transcriptomes of hepatocellular carcinomas identifies mutations and gene expression changes in the transforming growth factor-β pathway
  publication-title: Gastroenterology
– volume: 389
  start-page: 56
  year: 2017
  end-page: 66
  ident: CR2
  article-title: Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): A randomised, double-blind, placebo-controlled, phase 3 trial
  publication-title: Lancet
  doi: 10.1016/S0140-6736(16)32453-9
– volume: 379
  start-page: 54
  year: 2018
  end-page: 63
  ident: CR3
  article-title: Cabozantinib in patients with advanced and progressing hepatocellular carcinoma
  publication-title: N. Engl. J. Med.
  doi: 10.1056/NEJMoa1717002
– ident: CR7
– volume: 68
  start-page: 79
  year: 2011
  end-page: 86
  ident: CR20
  article-title: Kinase activation profile associated with TGF-β-dependent migration of HCC cells: a preclinical study
  publication-title: Cancer Chemother. Pharmacol.
– volume: 67
  start-page: 1503
  year: 2015
  end-page: 1513
  ident: CR42
  article-title: Lubricin/proteoglycan 4 binding to CD44 receptor: a mechanism of the suppression of proinflammatory cytokine-induced synoviocyte proliferation by lubricin
  publication-title: Arthritis Rheumatol.
  doi: 10.1002/art.39087
– volume: 20
  start-page: 4128
  year: 2014
  end-page: 4140
  ident: CR8
  article-title: Role of the tissue microenvironment as a therapeutic target in hepatocellular carcinoma
  publication-title: World J. Gastroenterol.
  doi: 10.3748/wjg.v20.i15.4128
– volume: 21
  start-page: 1786
  year: 2015
  ident: 3180_CR5
  publication-title: Clin. Cancer Res.
  doi: 10.1158/1078-0432.CCR-14-2602
– volume: 67
  start-page: 1261
  year: 2015
  ident: 3180_CR48
  publication-title: Arthritis Rheumatol.
  doi: 10.1002/art.39030
– volume: 379
  start-page: 54
  year: 2018
  ident: 3180_CR3
  publication-title: N. Engl. J. Med.
  doi: 10.1056/NEJMoa1717002
– volume: 63
  start-page: 1668
  year: 2014
  ident: 3180_CR9
  publication-title: Gut
  doi: 10.1136/gutjnl-2014-307323
– volume: 67
  start-page: 1503
  year: 2015
  ident: 3180_CR42
  publication-title: Arthritis Rheumatol.
  doi: 10.1002/art.39087
– volume: 136
  start-page: E161
  year: 2015
  ident: 3180_CR27
  publication-title: Int. J. Cancer
  doi: 10.1002/ijc.29097
– volume: 40
  start-page: 414
  year: 1998
  ident: 3180_CR28
  publication-title: J. Biomed. Mater. Res.
  doi: 10.1002/(SICI)1097-4636(19980605)40:3<414::AID-JBM11>3.0.CO;2-J
– volume: 116
  start-page: 109032
  year: 2019
  ident: 3180_CR60
  publication-title: Biomed. Pharmacother.
  doi: 10.1016/j.biopha.2019.109032
– volume: 391
  start-page: 1163
  year: 2018
  ident: 3180_CR1
  publication-title: Lancet
  doi: 10.1016/S0140-6736(18)30207-1
– volume: 34
  start-page: S1
  year: 2016
  ident: 3180_CR44
  publication-title: J. Orthop. Res.
  doi: 10.1002/jor.23247
– volume: 392
  start-page: 39
  year: 2017
  ident: 3180_CR26
  publication-title: Cancer Lett.
  doi: 10.1016/j.canlet.2017.01.037
– volume: 283
  start-page: 2219
  year: 2016
  ident: 3180_CR53
  publication-title: FEBS J.
  doi: 10.1111/febs.13665
– ident: 3180_CR7
  doi: 10.1007/978-3-030-21540-8_14
– volume: 63
  start-page: 269
  year: 2005
  ident: 3180_CR15
  publication-title: Prostate
  doi: 10.1002/pros.20182
– volume: 33
  start-page: 1061
  year: 2018
  ident: 3180_CR25
  publication-title: Cancer Cell
  doi: 10.1016/j.ccell.2018.05.003
– volume: 62
  start-page: 31
  year: 2020
  ident: 3180_CR13
  publication-title: Semin. Cancer Biol.
  doi: 10.1016/j.semcancer.2019.07.026
– volume: 114
  start-page: 183
  year: 2012
  ident: 3180_CR40
  publication-title: Oral. Surg. Oral. Med. Oral. Pathol. Oral. Radiol.
  doi: 10.1016/j.tripleo.2011.07.001
– volume: 28
  start-page: 71
  year: 1992
  ident: 3180_CR30
  publication-title: Connect. Tissue Res.
  doi: 10.3109/03008209209014228
– volume: 9
  year: 2018
  ident: 3180_CR22
  publication-title: Cell Death Dis.
  doi: 10.1038/s41419-018-0384-5
– volume: 154
  start-page: 195
  year: 2018
  ident: 3180_CR57
  publication-title: Gastroenterology
  doi: 10.1053/j.gastro.2017.09.007
– volume: 93
  start-page: 463
  year: 2004
  ident: 3180_CR16
  publication-title: J. Cell Biochem.
  doi: 10.1002/jcb.20189
– volume: 5
  start-page: 18
  year: 2017
  ident: 3180_CR24
  publication-title: Front. Cell Dev. Biol.
  doi: 10.3389/fcell.2017.00018
– volume: 46
  start-page: 1801
  year: 2007
  ident: 3180_CR36
  publication-title: Hepatology
  doi: 10.1002/hep.21936
– volume: 16
  year: 2015
  ident: 3180_CR31
  publication-title: BMC Musculoskelet. Disord.
  doi: 10.1186/s12891-015-0842-5
– volume: 8
  year: 2017
  ident: 3180_CR52
  publication-title: Cell Death Dis.
  doi: 10.1038/cddis.2017.469
– volume: 14
  start-page: e0219697
  year: 2019
  ident: 3180_CR23
  publication-title: PLoS ONE
  doi: 10.1371/journal.pone.0219697
– volume: 67
  start-page: 1222
  year: 2017
  ident: 3180_CR6
  publication-title: J. Hepatol.
  doi: 10.1016/j.jhep.2017.08.013
– volume: 115
  start-page: 622
  year: 2005
  ident: 3180_CR45
  publication-title: J. Clin. Invest.
  doi: 10.1172/JCI200522263
– volume: 19
  start-page: 89
  year: 2017
  ident: 3180_CR58
  publication-title: Arthritis Res. Ther.
  doi: 10.1186/s13075-017-1301-5
– volume: 27
  start-page: 594
  year: 2000
  ident: 3180_CR29
  publication-title: J. Rheumatol.
– volume: 47
  start-page: 1557
  year: 2008
  ident: 3180_CR17
  publication-title: Hepatology
  doi: 10.1002/hep.22201
– volume: 292
  start-page: 10465
  year: 2017
  ident: 3180_CR55
  publication-title: J. Biol. Chem.
  doi: 10.1074/jbc.M116.752451
– volume: 19
  start-page: 1172
  year: 2017
  ident: 3180_CR54
  publication-title: Curr. Protein Pept. Sci.
  doi: 10.2174/1389203718666171117112619
– volume: 8
  start-page: 29785
  year: 2017
  ident: 3180_CR56
  publication-title: Oncotarget
  doi: 10.18632/oncotarget.14523
– volume: 47
  start-page: 2059
  year: 2008
  ident: 3180_CR37
  publication-title: Hepatology
  doi: 10.1002/hep.22283
– volume: 50
  start-page: 1140
  year: 2009
  ident: 3180_CR19
  publication-title: Hepatology
  doi: 10.1002/hep.23118
– volume: 278
  start-page: 145
  year: 2009
  ident: 3180_CR59
  publication-title: Cancer Lett.
  doi: 10.1016/j.canlet.2008.12.031
– volume: 56
  start-page: 3662
  year: 2007
  ident: 3180_CR43
  publication-title: Arthritis Rheum.
  doi: 10.1002/art.22974
– volume: 23
  start-page: 319
  year: 1999
  ident: 3180_CR47
  publication-title: Nat. Genet.
  doi: 10.1038/15496
– volume: 65
  start-page: 861
  year: 2016
  ident: 3180_CR50
  publication-title: Gut
  doi: 10.1136/gutjnl-2014-308483
– volume: 14
  start-page: e0210601
  year: 2019
  ident: 3180_CR34
  publication-title: PLoS ONE
  doi: 10.1371/journal.pone.0210601
– volume: 1865
  start-page: 494
  year: 2019
  ident: 3180_CR49
  publication-title: Biochim. Biophys. Acta - Mol. Basis Dis.
  doi: 10.1016/j.bbadis.2018.11.009
– volume: 54
  start-page: 920
  year: 2011
  ident: 3180_CR10
  publication-title: Hepatology
  doi: 10.1002/hep.24485
– volume: 68
  start-page: 79
  year: 2011
  ident: 3180_CR20
  publication-title: Cancer Chemother. Pharmacol.
  doi: 10.1007/s00280-010-1459-x
– volume: 11
  start-page: 985
  year: 2019
  ident: 3180_CR4
  publication-title: Cancers (Basel)
  doi: 10.3390/cancers11070985
– volume: 38
  start-page: BSR20171264
  year: 2018
  ident: 3180_CR61
  publication-title: Biosci. Rep.
  doi: 10.1042/BSR20171264
– volume: 39
  start-page: 1468
  year: 2019
  ident: 3180_CR21
  publication-title: Liver Int.
  doi: 10.1111/liv.14113
– volume: 6
  year: 2016
  ident: 3180_CR38
  publication-title: Sci. Rep.
  doi: 10.1038/srep18910
– volume: 58
  start-page: 47
  year: 2006
  ident: 3180_CR14
  publication-title: IUBMB Life
  doi: 10.1080/15216540500531713
– volume: 79
  start-page: 3797
  year: 2019
  ident: 3180_CR51
  publication-title: Cancer Res.
  doi: 10.1158/0008-5472.CAN-18-2019
– volume: 21
  start-page: 1973
  year: 2015
  ident: 3180_CR41
  publication-title: Tissue Eng. Part A
  doi: 10.1089/ten.tea.2014.0381
– volume: 20
  start-page: 4128
  year: 2014
  ident: 3180_CR8
  publication-title: World J. Gastroenterol.
  doi: 10.3748/wjg.v20.i15.4128
– volume: 64
  start-page: 3963
  year: 2012
  ident: 3180_CR33
  publication-title: Arthritis Rheum.
  doi: 10.1002/art.34674
– volume: 278
  start-page: 315
  year: 2018
  ident: 3180_CR46
  publication-title: Atherosclerosis
  doi: 10.1016/j.atherosclerosis.2018.06.883
– volume: 17
  start-page: 353
  year: 2015
  ident: 3180_CR39
  publication-title: Arthritis Res. Ther.
  doi: 10.1186/s13075-015-0877-x
– volume: 389
  start-page: 56
  year: 2017
  ident: 3180_CR2
  publication-title: Lancet
  doi: 10.1016/S0140-6736(16)32453-9
– volume: 49
  start-page: 839
  year: 2009
  ident: 3180_CR18
  publication-title: Hepatology
  doi: 10.1002/hep.22731
– volume: 311
  start-page: 144
  year: 1994
  ident: 3180_CR32
  publication-title: Arch. Biochem. Biophys.
  doi: 10.1006/abbi.1994.1219
– volume: 5
  start-page: 176ra34
  year: 2013
  ident: 3180_CR35
  publication-title: Sci. Transl. Med.
  doi: 10.1126/scitranslmed.3005409
– volume: 115
  start-page: 1100
  year: 2005
  ident: 3180_CR12
  publication-title: J. Clin. Invest.
  doi: 10.1172/JCI200524282C1
– volume: 51
  start-page: 523
  year: 2010
  ident: 3180_CR11
  publication-title: Hepatology
  doi: 10.1002/hep.23285
SSID ssj0000330256
Score 2.3816369
Snippet Sorafenib and regorafenib administration is among the preferential approaches to treat hepatocellular carcinoma (HCC), but does not provide satisfactory...
SourceID pubmedcentral
proquest
pubmed
crossref
springer
SourceType Open Access Repository
Aggregation Database
Index Database
Enrichment Source
Publisher
StartPage 984
SubjectTerms 13/1
13/106
13/109
13/31
13/51
13/95
38/109
38/77
631/67/1059/602
692/308/2778
Antibodies
Antineoplastic Combined Chemotherapy Protocols - pharmacology
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Biochemistry
Biomedical and Life Sciences
Carcinoma, Hepatocellular - drug therapy
Carcinoma, Hepatocellular - pathology
CD44 antigen
Cell adhesion & migration
Cell Biology
Cell Culture
Cell migration
Cell proliferation
Extracellular matrix
Fibroblasts
Hepatocellular carcinoma
Humans
Immunology
Inhibitor drugs
Life Sciences
Liver cancer
Liver Neoplasms - drug therapy
Liver Neoplasms - pathology
mRNA
Phenylurea Compounds - pharmacology
Phenylurea Compounds - therapeutic use
Proteoglycans
Proteoglycans - pharmacology
Proteoglycans - therapeutic use
Pyridines - pharmacology
Pyridines - therapeutic use
Sorafenib - pharmacology
Sorafenib - therapeutic use
Targeted cancer therapy
Transforming growth factor-b
Tumor Microenvironment
SummonAdditionalLinks – databaseName: Health & Medical Collection (ProQuest)
  dbid: 7X7
  link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwfV1La9wwEBZtSqGX0HfcpkGF3loRryVL8qmUbcJSaOmhgb0ZW4_GsMhJvBvIP-jP7oysddiGBp9sy7I9Mxp9I82DkA-NQtguY-bHkgnfOtaAJcRM5ZvS51b7GCT2_YdcnIlvy3KZFtyG5Fa51YlRUdve4Br5cQFatJQKbO7PF5cMq0bh7moqofGQPJoBEsHSDWqppjWWHIx1mNJTrEzO9fEgZgKjdsBmQmnOmd6dj-6AzLu-kv9smMZ56PQp2U8Akn4ZOf6MPHDhOXk8lpS8eUH-_MTEC_3v1Q3QjAnaDdRgAY4VYEpLcdWVrnrslw4b0BIgZ7QLdDGf05RhdaBNsNSFcxSHgQ4gIt6Fro2XY0BLOh89QZKypNddQ-dfhcDerrv1Vf-SnJ2e_JovWKq2wIxQYs1a0SoL6sZrLb2VGDtS-kLr0gjZADAApJQD9YxwVgqnWs25hwMURGXAjLb8FdkLfXAHhJqyLYBighfaA1yz2swaKVtvAC1x4XlGZlua1yalIseKGKs6bolzXY98qoFPdeRTrTPycXrmYkzEcW_rwy0r6zQoh_pWhDLyfroNwwn3SJrg-g22AXwDmLmCLl6PnJ9exzm6bKsqI2pHJqYGmKp7907ozmPKbiVlBXTNyKet9Nx-1v__4s39f_GWPClQktEpUR6SvfXVxr0DiLRuj-I4-AsgwQ5o
  priority: 102
  providerName: ProQuest
– databaseName: Springer Nature OA Free Journals
  dbid: C6C
  link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwlV1La9wwEB6SlEIuoa-0TtOiQm-tqdeSJfkY3Ial0NJDA7kZW5YawyKXeDeQf5CfnRn5EbZJC8UnW7Isz4xmPkkzI4D3lSLYLkPmxywWrrZxhTOh2OSuylzSaBeCxL59l8sz8fU8O9-BdIqFCU77IaVlUNOTd9inXiwEhdvgZIfEMIn1LjzSimck1YUs5nWVBCfoaMbH-JiE6wde3bZB94Dlff_IPzZJg-05fQIHI2hkJ0M3n8KO9c_g8XCM5PVzuPlByRa6X6trpFMsWNszQ4durBBHNoxWWtmqo3ZZv0HNgLLFWs-WRcHGrKo9q3zDrL8gEehZj2LhrG_r8DgEsYz3g_fHqCDZVVux4rMQ1NpVu77sXsDZ6ZefxTIeT1iIjVBiHdeiVg2qGKe1dI2keJHMpVpnRsgKwQCiowSpZ4RtpLCq1pw7vFAp5Aanzg0_hD3fefsKmMnqFCkmeKodQrRGm0UlZe0MIiQuHI9gMdG8NGP6cToFY1WGbXCuy4FPJfKpDHwqdQQf5nd-D8k3_ln7eGJlOQ7EvkzR-GZSLXIRwbu5GIcQ7YtU3nYbqoOYBnFyjk28HDg_f45zctNWeQRqSybmCpSee7vEtxchTbeSMke6RvBxkp67bv39L47-r_pr2E9JsskxUR7D3vpyY98gTFrXb8O4uAV7QAwc
  priority: 102
  providerName: Springer Nature
Title Proteoglycan-4 is correlated with longer survival in HCC patients and enhances sorafenib and regorafenib effectiveness via CD44 in vitro
URI https://link.springer.com/article/10.1038/s41419-020-03180-8
https://www.ncbi.nlm.nih.gov/pubmed/33199679
https://www.proquest.com/docview/2471567194
https://www.proquest.com/docview/2461399198
https://pubmed.ncbi.nlm.nih.gov/PMC7669886
Volume 11
hasFullText 1
inHoldings 1
isFullTextHit
isPrint
link http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwfV3db9MwED_tQ6C9THyTMSoj8QaBNnEc5wGhEjpVlZgmoFLfosSxt0hRAk070Ree-bO5c5LC2IYqtWriuOn55_Pv4vsAeJmGRNuFzfwYuNxk2k3REnJVZNLADHNpbJDYp1MxnfPZIljsQF_uqBNgc6NpR_Wk5svyzY_vm_c44d-1IePybcNHnEJx0BAiiA5duQv7dr-IXPk6um81MxrvuMR3sTM3X3oAd32fXHPJuevvpeoa_7zuRvnPXqpdok7uwWHHLdm4BcN92NHVA7jTVpvcPIRfZ5SToT4vNyhOl7OiYYpqc5RIN3NGD2RZWVO_rFmjAkEIsqJi0zhmXfLVhqVVznR1QUhpWIPoMboqMnvYxrp031snkU6PsssiZfFHzqm3y2K1rB_B_GTyNZ66XSEGV_GQr9yMZ2GOmshIKUwuKKwkMJ6UgeIiRc6AJGqIglRc54LrMJO-b_CFuiNSaGHn_mPYq-pKPwWmgsxDiXHfkwaZXC7VKBUiMwqJlM-N78Col3miuizlVCyjTOxuuS-TdsgSHLLEDlkiHXi1veZbm6Pjv62P-6FMerglHq7RgQhHEXfgxfY0zjTaPkkrXa-pDVIfpNMRdvGkHfntz_WQcSC8goltA8riffVMVVzYbN6hEBHK1YHXPXr-3Nbt_-Lo1lt4Bgce4ZlcFcUx7K2Wa_0cidMqG8BuuAgHsD8ez77M8PPD5PTsMx6NRTywDyMGdr7Q-8_Jb02_GIU
linkProvider Scholars Portal
linkToHtml http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwtV1Lb9QwEB6VIgSXimdJKWAkOEHUbOzYzgEhtKXa0oc4tNLeQuLYNNIqKc1u0f4Dfg2_kZm8qqWit2pP2TjejefhbzwvgLepItgum8qPkS9cZv0ULSHfxC6NXJBr1ySJHR3Lyan4Oo2ma_Cnz4WhsMpeJzaKOq8MnZHvhKhFI6nQ5v50_tOnrlHkXe1baLRscWCXv9Bkqz_u7yJ934Xh3peT8cTvugr4Rigx9zORqRzFymktXS4pRyJyodaRETLFDRARQSBGwgibS2FVpjl3-EFBiA2aiznHee_AXUEuRpQfNVXDmU6AoxBCdLk5Adc7Nc5EWUJoo5H0BL5e3f-ugdrrsZn_OGibfW_vIWx0gJV9bjnsEazZ8jHca1tYLp_A729U6KH6MVsijXzBipoZavgxQwybMzrlZbOK5mX1ArUS8jUrSjYZj1lX0bVmaZkzW54R-9WsRpZ0tiyy5usmgaa7biNPOuXMLouUjXeFoNkui_lF9RROb4UOz2C9rEr7HJiJshBXTPBQO4SHuTajVMrMGURnXDjuwahf88R0pc-pA8csaVzwXCctnRKkU9LQKdEevB-eOW8Lf9w4ersnZdIpgTq5YlkP3gy3UXzJJ5OWtlrQGMRTiNFjnGKzpfzwc5xTiLiKPVArPDEMoNLgq3fK4qwpEa6kjHFdPfjQc8_V3_r_W2zd_Bav4f7k5OgwOdw_PngBD0LiagqIlNuwPr9Y2JcIz-bZq0YmGHy_bSH8CwQ2SQk
linkToPdf http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwtV1bb9MwFLbGJhAviDuBAUaCJ4iaxo7jPEwI2lUdg6pCTNpbSOyYRaqSsbRD_Qf8Nn4V5zhOpjKxt6lPaZzTxufi79jnQsjrLEbYLmzlx8jnJi_8DDwhXyUmi0ygpbFJYl9mYnrEPx1Hx1vkT5cLg2GVnU20hlrXCvfIByFY0UjE4HMPjAuLmI8n709_-thBCk9au3YamWuzoPdsuTGX5HFYrH-BO9fsHYyB92_CcLL_bTT1XccBX_GYL_2c57EGlTNSCqMF5k9EJpQyUlxksDgCWgj4kCteaMGLOJeMGfiAkiQKXEnNgO4NshPDqg-O4M7H_dn8a7_jE8A4ABgucydgctAALcwhAg8OdSvw5ebqeAnyXo7c_Of41q6Kk7vkjoOz9EMrf_fIVlHdJzfbBpfrB-T3HMtA1D8Wa-Cgz2nZUIXtQBaAcDXFPWC6qJEubVZgs0DqaVnR6WhEXb3XhmaVpkV1gsLZ0AYE1hRVmduvbXqNu27jUpzppudlRkdjzpHaebk8qx-So2vhxCOyXdVV8YRQFeUhzBhnoTQAHrVUw0yI3CjAbowb5pFhN-epcoXRsT_HIrUH9EymLZ9S4FNq-ZRKj7ztnzlty4JcOXq3Y2XqTESTXgi0R171t0G58cQmq4p6hWMAbQGCT4DE45bz_c8xhgHkceKReEMm-gFYOHzzTlWe2ALisRAJzKtH3nXSc_G3_v8WT69-i5fkFihk-vlgdviM3A5RqDFaUuyS7eXZqngO2G2Zv3BKQcn369bDv6qkU-Q
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Proteoglycan-4+is+correlated+with+longer+survival+in+HCC+patients+and+enhances+sorafenib+and+regorafenib+effectiveness+via+CD44+in+vitro&rft.jtitle=Cell+death+%26+disease&rft.au=Dituri%2C+Francesco&rft.au=Scialpi%2C+Rosanna&rft.au=Schmidt%2C+Tannin+A&rft.au=Frusciante%2C+Martina&rft.date=2020-11-16&rft.eissn=2041-4889&rft.volume=11&rft.issue=11&rft.spage=984&rft_id=info:doi/10.1038%2Fs41419-020-03180-8&rft_id=info%3Apmid%2F33199679&rft.externalDocID=33199679
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=2041-4889&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=2041-4889&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=2041-4889&client=summon