Heparan sulfate proteoglycans and heparin regulate melanoma cell functions

The solid melanoma tumor consists of transformed melanoma cells, and the associated stromal cells including fibroblasts, endothelial cells, immune cells, as well as, soluble macro- and micro-molecules of the extracellular matrix (ECM) forming the complex network of the tumor microenvironment. Hepara...

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Published in	Biochimica et biophysica acta Vol. 1840; no. 8; pp. 2471 - 2481
Main Authors	Nikitovic, D., Mytilinaiou, M., Berdiaki, Ai, Karamanos, N.K., Tzanakakis, G.N.
Format	Journal Article
Language	English
Published	Netherlands Elsevier B.V 01.08.2014
Subjects	Animals Cell function Disease Progression endothelial cells extracellular matrix Extracellular Matrix - metabolism fibroblasts heparan sulfate Heparan sulfate proteoglycan Heparan Sulfate Proteoglycans - metabolism Heparin Heparin - metabolism Humans Melanoma Melanoma - genetics Melanoma - metabolism Melanoma - pathology Melanoma - therapy proteoglycans Signal Transduction - genetics stromal cells therapeutics HSPG Cell function MMPs Melanoma FN HS GAG ECM CS SDC PG GPC Heparin Heparan sulfate proteoglycan
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ISSN	0304-4165 0006-3002 1872-8006
DOI	10.1016/j.bbagen.2014.01.031

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Abstract	The solid melanoma tumor consists of transformed melanoma cells, and the associated stromal cells including fibroblasts, endothelial cells, immune cells, as well as, soluble macro- and micro-molecules of the extracellular matrix (ECM) forming the complex network of the tumor microenvironment. Heparan sulfate proteoglycans (HSPGs) are an important component of the melanoma tumor ECM. Importantly, there appears to be both a quantitative and a qualitative shift in the content of HSPGs, in parallel to the nevi–radial growth phase–vertical growth phase melanoma progression. Moreover, these changes in HSPG expression are correlated to modulations of key melanoma cell functions. This review will critically discuss the roles of HSPGs/heparin in melanoma development and progression. We have correlated HSPGs' expression and distribution with melanoma cell signaling and functions as well as angiogenesis. The current knowledge of HSPGs/heparin biology in melanoma provides a foundation we can utilize in the ongoing search for new approaches in designing anti-tumor therapy. This article is part of a Special Issue entitled Matrix-mediated cell behaviour and properties. •Melanoma is a highly metastatic tumor with fatal complications.•There are distinct quality variations in melanoma ECM.•HSPGs are strongly involved in melanoma cell functions through their fine structure.•HSPGs could be potential therapeutic targets against melanoma progression.
AbstractList	The solid melanoma tumor consists of transformed melanoma cells, and the associated stromal cells including fibroblasts, endothelial cells, immune cells, as well as, soluble macro- and micro-molecules of the extracellular matrix (ECM) forming the complex network of the tumor microenvironment. Heparan sulfate proteoglycans (HSPGs) are an important component of the melanoma tumor ECM. Importantly, there appears to be both a quantitative and a qualitative shift in the content of HSPGs, in parallel to the nevi–radial growth phase–vertical growth phase melanoma progression. Moreover, these changes in HSPG expression are correlated to modulations of key melanoma cell functions. This review will critically discuss the roles of HSPGs/heparin in melanoma development and progression. We have correlated HSPGs' expression and distribution with melanoma cell signaling and functions as well as angiogenesis. The current knowledge of HSPGs/heparin biology in melanoma provides a foundation we can utilize in the ongoing search for new approaches in designing anti-tumor therapy. This article is part of a Special Issue entitled Matrix-mediated cell behaviour and properties. •Melanoma is a highly metastatic tumor with fatal complications.•There are distinct quality variations in melanoma ECM.•HSPGs are strongly involved in melanoma cell functions through their fine structure.•HSPGs could be potential therapeutic targets against melanoma progression. The solid melanoma tumor consists of transformed melanoma cells, and the associated stromal cells including fibroblasts, endothelial cells, immune cells, as well as, soluble macro- and micro-molecules of the extracellular matrix (ECM) forming the complex network of the tumor microenvironment. Heparan sulfate proteoglycans (HSPGs) are an important component of the melanoma tumor ECM. Importantly, there appears to be both a quantitative and a qualitative shift in the content of HSPGs, in parallel to the nevi–radial growth phase–vertical growth phase melanoma progression. Moreover, these changes in HSPG expression are correlated to modulations of key melanoma cell functions.This review will critically discuss the roles of HSPGs/heparin in melanoma development and progression.We have correlated HSPGs' expression and distribution with melanoma cell signaling and functions as well as angiogenesis.The current knowledge of HSPGs/heparin biology in melanoma provides a foundation we can utilize in the ongoing search for new approaches in designing anti-tumor therapy. This article is part of a Special Issue entitled Matrix-mediated cell behaviour and properties. The solid melanoma tumor consists of transformed melanoma cells, and the associated stromal cells including fibroblasts, endothelial cells, immune cells, as well as, soluble macro- and micro-molecules of the extracellular matrix (ECM) forming the complex network of the tumor microenvironment. Heparan sulfate proteoglycans (HSPGs) are an important component of the melanoma tumor ECM. Importantly, there appears to be both a quantitative and a qualitative shift in the content of HSPGs, in parallel to the nevi-radial growth phase-vertical growth phase melanoma progression. Moreover, these changes in HSPG expression are correlated to modulations of key melanoma cell functions. This review will critically discuss the roles of HSPGs/heparin in melanoma development and progression. We have correlated HSPGs' expression and distribution with melanoma cell signaling and functions as well as angiogenesis. The current knowledge of HSPGs/heparin biology in melanoma provides a foundation we can utilize in the ongoing search for new approaches in designing anti-tumor therapy. This article is part of a Special Issue entitled Matrix-mediated cell behaviour and properties. The solid melanoma tumor consists of transformed melanoma cells, and the associated stromal cells including fibroblasts, endothelial cells, immune cells, as well as, soluble macro- and micro-molecules of the extracellular matrix (ECM) forming the complex network of the tumor microenvironment. Heparan sulfate proteoglycans (HSPGs) are an important component of the melanoma tumor ECM. Importantly, there appears to be both a quantitative and a qualitative shift in the content of HSPGs, in parallel to the nevi-radial growth phase-vertical growth phase melanoma progression. Moreover, these changes in HSPG expression are correlated to modulations of key melanoma cell functions.BACKGROUNDThe solid melanoma tumor consists of transformed melanoma cells, and the associated stromal cells including fibroblasts, endothelial cells, immune cells, as well as, soluble macro- and micro-molecules of the extracellular matrix (ECM) forming the complex network of the tumor microenvironment. Heparan sulfate proteoglycans (HSPGs) are an important component of the melanoma tumor ECM. Importantly, there appears to be both a quantitative and a qualitative shift in the content of HSPGs, in parallel to the nevi-radial growth phase-vertical growth phase melanoma progression. Moreover, these changes in HSPG expression are correlated to modulations of key melanoma cell functions.This review will critically discuss the roles of HSPGs/heparin in melanoma development and progression.SCOPE OF REVIEWThis review will critically discuss the roles of HSPGs/heparin in melanoma development and progression.We have correlated HSPGs' expression and distribution with melanoma cell signaling and functions as well as angiogenesis.MAJOR CONCLUSIONSWe have correlated HSPGs' expression and distribution with melanoma cell signaling and functions as well as angiogenesis.The current knowledge of HSPGs/heparin biology in melanoma provides a foundation we can utilize in the ongoing search for new approaches in designing anti-tumor therapy. This article is part of a Special Issue entitled Matrix-mediated cell behaviour and properties.GENERAL SIGNIFICANCEThe current knowledge of HSPGs/heparin biology in melanoma provides a foundation we can utilize in the ongoing search for new approaches in designing anti-tumor therapy. This article is part of a Special Issue entitled Matrix-mediated cell behaviour and properties.
Author	Karamanos, N.K. Mytilinaiou, M. Tzanakakis, G.N. Nikitovic, D. Berdiaki, Ai
Author_xml	– sequence: 1 givenname: D. surname: Nikitovic fullname: Nikitovic, D. organization: Department of Anatomy, Histology, Embryology, Medical School, University of Crete, Heraklion 71003, Greece – sequence: 2 givenname: M. surname: Mytilinaiou fullname: Mytilinaiou, M. organization: Department of Anatomy, Histology, Embryology, Medical School, University of Crete, Heraklion 71003, Greece – sequence: 3 givenname: Ai surname: Berdiaki fullname: Berdiaki, Ai organization: Department of Anatomy, Histology, Embryology, Medical School, University of Crete, Heraklion 71003, Greece – sequence: 4 givenname: N.K. surname: Karamanos fullname: Karamanos, N.K. organization: Laboratory of Biochemistry, Department of Chemistry, University of Patras, Patras 26110, Greece – sequence: 5 givenname: G.N. surname: Tzanakakis fullname: Tzanakakis, G.N. email: tzanakak@med.uoc.gr organization: Department of Anatomy, Histology, Embryology, Medical School, University of Crete, Heraklion 71003, Greece
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/24486410$$D View this record in MEDLINE/PubMed
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Snippet	The solid melanoma tumor consists of transformed melanoma cells, and the associated stromal cells including fibroblasts, endothelial cells, immune cells, as...
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SubjectTerms	Animals Cell function Disease Progression endothelial cells extracellular matrix Extracellular Matrix - metabolism fibroblasts heparan sulfate Heparan sulfate proteoglycan Heparan Sulfate Proteoglycans - metabolism Heparin Heparin - metabolism Humans Melanoma Melanoma - genetics Melanoma - metabolism Melanoma - pathology Melanoma - therapy proteoglycans Signal Transduction - genetics stromal cells therapeutics
Title	Heparan sulfate proteoglycans and heparin regulate melanoma cell functions
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