ITLN1 modulates invasive potential and metabolic reprogramming of ovarian cancer cells in omental microenvironment
Advanced ovarian cancer usually spreads to the omentum. However, the omental cell-derived molecular determinants modulating its progression have not been thoroughly characterized. Here, we show that circulating ITLN1 has prognostic significance in patients with advanced ovarian cancer. Further studi...
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| Published in | Nature communications Vol. 11; no. 1; pp. 3546 - 16 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
London
Nature Publishing Group UK
15.07.2020
Nature Publishing Group Nature Portfolio |
| Subjects | |
| Online Access | Get full text |
| ISSN | 2041-1723 2041-1723 |
| DOI | 10.1038/s41467-020-17383-2 |
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| Abstract | Advanced ovarian cancer usually spreads to the omentum. However, the omental cell-derived molecular determinants modulating its progression have not been thoroughly characterized. Here, we show that circulating ITLN1 has prognostic significance in patients with advanced ovarian cancer. Further studies demonstrate that ITLN1 suppresses lactotransferrin’s effect on ovarian cancer cell invasion potential and proliferation by decreasing MMP1 expression and inducing a metabolic shift in metastatic ovarian cancer cells. Additionally, ovarian cancer-bearing mice treated with ITLN1 demonstrate marked decrease in tumor growth rates. These data suggest that downregulation of mesothelial cell-derived ITLN1 in the omental tumor microenvironment facilitates ovarian cancer progression.
Advanced ovarian cancer usually spreads to the omentum. Here, the authors show that circulating intelectin-1 (ITLN1) has prognostic significance in patients with advanced ovarian cancer, and that mesothelial cell-derived ITLN1 in the omental tumor microenvironment suppresses ovarian cancer progression. |
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| AbstractList | Advanced ovarian cancer usually spreads to the omentum. However, the omental cell-derived molecular determinants modulating its progression have not been thoroughly characterized. Here, we show that circulating ITLN1 has prognostic significance in patients with advanced ovarian cancer. Further studies demonstrate that ITLN1 suppresses lactotransferrin’s effect on ovarian cancer cell invasion potential and proliferation by decreasing MMP1 expression and inducing a metabolic shift in metastatic ovarian cancer cells. Additionally, ovarian cancer-bearing mice treated with ITLN1 demonstrate marked decrease in tumor growth rates. These data suggest that downregulation of mesothelial cell-derived ITLN1 in the omental tumor microenvironment facilitates ovarian cancer progression.Advanced ovarian cancer usually spreads to the omentum. Here, the authors show that circulating intelectin-1 (ITLN1) has prognostic significance in patients with advanced ovarian cancer, and that mesothelial cell-derived ITLN1 in the omental tumor microenvironment suppresses ovarian cancer progression. Advanced ovarian cancer usually spreads to the omentum. However, the omental cell-derived molecular determinants modulating its progression have not been thoroughly characterized. Here, we show that circulating ITLN1 has prognostic significance in patients with advanced ovarian cancer. Further studies demonstrate that ITLN1 suppresses lactotransferrin's effect on ovarian cancer cell invasion potential and proliferation by decreasing MMP1 expression and inducing a metabolic shift in metastatic ovarian cancer cells. Additionally, ovarian cancer-bearing mice treated with ITLN1 demonstrate marked decrease in tumor growth rates. These data suggest that downregulation of mesothelial cell-derived ITLN1 in the omental tumor microenvironment facilitates ovarian cancer progression.Advanced ovarian cancer usually spreads to the omentum. However, the omental cell-derived molecular determinants modulating its progression have not been thoroughly characterized. Here, we show that circulating ITLN1 has prognostic significance in patients with advanced ovarian cancer. Further studies demonstrate that ITLN1 suppresses lactotransferrin's effect on ovarian cancer cell invasion potential and proliferation by decreasing MMP1 expression and inducing a metabolic shift in metastatic ovarian cancer cells. Additionally, ovarian cancer-bearing mice treated with ITLN1 demonstrate marked decrease in tumor growth rates. These data suggest that downregulation of mesothelial cell-derived ITLN1 in the omental tumor microenvironment facilitates ovarian cancer progression. Advanced ovarian cancer usually spreads to the omentum. Here, the authors show that circulating intelectin-1 (ITLN1) has prognostic significance in patients with advanced ovarian cancer, and that mesothelial cell-derived ITLN1 in the omental tumor microenvironment suppresses ovarian cancer progression. Advanced ovarian cancer usually spreads to the omentum. However, the omental cell-derived molecular determinants modulating its progression have not been thoroughly characterized. Here, we show that circulating ITLN1 has prognostic significance in patients with advanced ovarian cancer. Further studies demonstrate that ITLN1 suppresses lactotransferrin’s effect on ovarian cancer cell invasion potential and proliferation by decreasing MMP1 expression and inducing a metabolic shift in metastatic ovarian cancer cells. Additionally, ovarian cancer-bearing mice treated with ITLN1 demonstrate marked decrease in tumor growth rates. These data suggest that downregulation of mesothelial cell-derived ITLN1 in the omental tumor microenvironment facilitates ovarian cancer progression. Advanced ovarian cancer usually spreads to the omentum. Here, the authors show that circulating intelectin-1 (ITLN1) has prognostic significance in patients with advanced ovarian cancer, and that mesothelial cell-derived ITLN1 in the omental tumor microenvironment suppresses ovarian cancer progression. Advanced ovarian cancer usually spreads to the omentum. However, the omental cell-derived molecular determinants modulating its progression have not been thoroughly characterized. Here, we show that circulating ITLN1 has prognostic significance in patients with advanced ovarian cancer. Further studies demonstrate that ITLN1 suppresses lactotransferrin’s effect on ovarian cancer cell invasion potential and proliferation by decreasing MMP1 expression and inducing a metabolic shift in metastatic ovarian cancer cells. Additionally, ovarian cancer-bearing mice treated with ITLN1 demonstrate marked decrease in tumor growth rates. These data suggest that downregulation of mesothelial cell-derived ITLN1 in the omental tumor microenvironment facilitates ovarian cancer progression. |
| ArticleNumber | 3546 |
| Author | Zhu, Ying Yip, Kay-Pong Mok, Samuel C. Schmandt, Rosemarie Kwan, Suet-Ying Achreja, Abhinav Rynne-Vidal, Angela Wong, Stephen T. C. Zhao, Hongyun Onstad, Michaela Baluya, Dodge L. Lu, Karen H. Yeung, Tsz-Lun Sheng, Jianting Co, Ngai-Na Anderson, Matthew L. Nagrath, Deepak Au-Yeung, Chi-Lam |
| Author_xml | – sequence: 1 givenname: Chi-Lam surname: Au-Yeung fullname: Au-Yeung, Chi-Lam email: cau@mdanderson.org organization: Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences at Houston – sequence: 2 givenname: Tsz-Lun surname: Yeung fullname: Yeung, Tsz-Lun organization: Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences at Houston – sequence: 3 givenname: Abhinav orcidid: 0000-0002-1773-6490 surname: Achreja fullname: Achreja, Abhinav organization: Department of Biomedical Engineering, University of Michigan – sequence: 4 givenname: Hongyun surname: Zhao fullname: Zhao, Hongyun organization: Department of Biomedical Engineering, University of Michigan – sequence: 5 givenname: Kay-Pong surname: Yip fullname: Yip, Kay-Pong organization: Department of Molecular Pharmacology and Physiology, University of South Florida – sequence: 6 givenname: Suet-Ying surname: Kwan fullname: Kwan, Suet-Ying organization: Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center – sequence: 7 givenname: Michaela surname: Onstad fullname: Onstad, Michaela organization: Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center – sequence: 8 givenname: Jianting surname: Sheng fullname: Sheng, Jianting organization: Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, Weill Cornell Medicine, Center for Precision Oncology, Houston Methodist Cancer Center – sequence: 9 givenname: Ying surname: Zhu fullname: Zhu, Ying organization: Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, Weill Cornell Medicine, Center for Precision Oncology, Houston Methodist Cancer Center – sequence: 10 givenname: Dodge L. surname: Baluya fullname: Baluya, Dodge L. organization: Department of Diagnostic Imaging-Interventional Radiology, The University of Texas MD Anderson Cancer Center – sequence: 11 givenname: Ngai-Na surname: Co fullname: Co, Ngai-Na organization: Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center – sequence: 12 givenname: Angela orcidid: 0000-0002-6316-530X surname: Rynne-Vidal fullname: Rynne-Vidal, Angela organization: Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center – sequence: 13 givenname: Rosemarie surname: Schmandt fullname: Schmandt, Rosemarie organization: Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences at Houston – sequence: 14 givenname: Matthew L. orcidid: 0000-0002-2081-4672 surname: Anderson fullname: Anderson, Matthew L. organization: Department of Obstetrics and Gynecology, Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine – sequence: 15 givenname: Karen H. surname: Lu fullname: Lu, Karen H. organization: Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences at Houston – sequence: 16 givenname: Stephen T. C. surname: Wong fullname: Wong, Stephen T. C. organization: Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, Weill Cornell Medicine, Center for Precision Oncology, Houston Methodist Cancer Center – sequence: 17 givenname: Deepak orcidid: 0000-0002-8999-2282 surname: Nagrath fullname: Nagrath, Deepak email: dnagrath@umich.edu organization: Department of Biomedical Engineering, University of Michigan – sequence: 18 givenname: Samuel C. orcidid: 0000-0001-7013-1805 surname: Mok fullname: Mok, Samuel C. email: scmok@mdanderson.org organization: Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences at Houston |
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| Snippet | Advanced ovarian cancer usually spreads to the omentum. However, the omental cell-derived molecular determinants modulating its progression have not been... Advanced ovarian cancer usually spreads to the omentum. Here, the authors show that circulating intelectin-1 (ITLN1) has prognostic significance in patients... |
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| SubjectTerms | 13/51 49/61 49/88 49/91 59/5 631/67/1517/1709 64/60 692/53/2422 Animals Cancer Carcinoma, Ovarian Epithelial - blood Carcinoma, Ovarian Epithelial - mortality Carcinoma, Ovarian Epithelial - secondary Carcinoma, Ovarian Epithelial - therapy Cell Line, Tumor - transplantation Cell Movement Cell Proliferation Cell Transformation, Neoplastic - metabolism Cytokines - administration & dosage Cytokines - blood Cytokines - metabolism Disease Models, Animal Down-Regulation Female Gene Expression Regulation, Neoplastic GPI-Linked Proteins - administration & dosage GPI-Linked Proteins - blood GPI-Linked Proteins - metabolism Growth rate Health risk assessment Humanities and Social Sciences Humans Invasiveness Lactoferrin - metabolism Lectins - administration & dosage Lectins - blood Lectins - metabolism Matrix Metalloproteinase 1 - metabolism Metabolism Metastases Mice multidisciplinary Neoplasm Invasiveness - pathology Omentum Omentum - pathology Ovarian cancer Ovarian Neoplasms - blood Ovarian Neoplasms - mortality Ovarian Neoplasms - pathology Ovarian Neoplasms - therapy Ovary Peritoneal Neoplasms - secondary Recombinant Proteins - administration & dosage Science Science (multidisciplinary) Survival Rate Tumor Microenvironment Tumors |
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| Title | ITLN1 modulates invasive potential and metabolic reprogramming of ovarian cancer cells in omental microenvironment |
| URI | https://link.springer.com/article/10.1038/s41467-020-17383-2 https://www.ncbi.nlm.nih.gov/pubmed/32669559 https://www.proquest.com/docview/2423961938 https://www.proquest.com/docview/2424444307 https://pubmed.ncbi.nlm.nih.gov/PMC7363861 https://doaj.org/article/a6dd5cbe55934dbcaae176ed33be66a7 |
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