Cargando…
TIMP-1 Is Overexpressed and Secreted by Platinum Resistant Epithelial Ovarian Cancer Cells
Epithelial Ovarian Cancer (EOC) is the most lethal gynecological cancer in developed countries, and the development of new strategies to overcome chemoresistance is an awaited clinical need. Angiogenesis, the development of new blood vessels from pre-existing vasculature, has been validated as a the...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016675/ https://www.ncbi.nlm.nih.gov/pubmed/31861382 http://dx.doi.org/10.3390/cells9010006 |
_version_ | 1783497029633179648 |
---|---|
author | Sonego, Maura Poletto, Evelina Pivetta, Eliana Nicoloso, Milena S. Pellicani, Rosanna Rampioni Vinciguerra, Gian Luca Citron, Francesca Sorio, Roberto Mongiat, Maurizio Baldassarre, Gustavo |
author_facet | Sonego, Maura Poletto, Evelina Pivetta, Eliana Nicoloso, Milena S. Pellicani, Rosanna Rampioni Vinciguerra, Gian Luca Citron, Francesca Sorio, Roberto Mongiat, Maurizio Baldassarre, Gustavo |
author_sort | Sonego, Maura |
collection | PubMed |
description | Epithelial Ovarian Cancer (EOC) is the most lethal gynecological cancer in developed countries, and the development of new strategies to overcome chemoresistance is an awaited clinical need. Angiogenesis, the development of new blood vessels from pre-existing vasculature, has been validated as a therapeutic target in this tumor type. The aim of this study is to verify if EOC cells with acquired resistance to platinum (PT) treatment display an altered angiogenic potential. Using a proteomic approach, we identified the tissue inhibitor of metalloproteinases 1 (TIMP-1) as the only secreted factor whose expression was up-regulated in PT-resistant TOV-112D and OVSAHO EOC cells used as study models. We report that TIMP-1 acts as a double-edged sword in the EOC microenvironment, directly affecting the response to PT treatment on tumor cells and indirectly altering migration and proliferation of endothelial cells. Interestingly, we found that high TIMP-1 levels in stage III–IV EOC patients associate with decreased overall survival, especially if they were treated with PT or bevacizumab. Taken together, these results pinpoint TIMP-1 as a key molecule involved in the regulation of EOC PT-resistance and progression disclosing the possibility that it could be used as a new biomarker of PT-resistance and/or therapeutic target. |
format | Online Article Text |
id | pubmed-7016675 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-70166752020-02-28 TIMP-1 Is Overexpressed and Secreted by Platinum Resistant Epithelial Ovarian Cancer Cells Sonego, Maura Poletto, Evelina Pivetta, Eliana Nicoloso, Milena S. Pellicani, Rosanna Rampioni Vinciguerra, Gian Luca Citron, Francesca Sorio, Roberto Mongiat, Maurizio Baldassarre, Gustavo Cells Article Epithelial Ovarian Cancer (EOC) is the most lethal gynecological cancer in developed countries, and the development of new strategies to overcome chemoresistance is an awaited clinical need. Angiogenesis, the development of new blood vessels from pre-existing vasculature, has been validated as a therapeutic target in this tumor type. The aim of this study is to verify if EOC cells with acquired resistance to platinum (PT) treatment display an altered angiogenic potential. Using a proteomic approach, we identified the tissue inhibitor of metalloproteinases 1 (TIMP-1) as the only secreted factor whose expression was up-regulated in PT-resistant TOV-112D and OVSAHO EOC cells used as study models. We report that TIMP-1 acts as a double-edged sword in the EOC microenvironment, directly affecting the response to PT treatment on tumor cells and indirectly altering migration and proliferation of endothelial cells. Interestingly, we found that high TIMP-1 levels in stage III–IV EOC patients associate with decreased overall survival, especially if they were treated with PT or bevacizumab. Taken together, these results pinpoint TIMP-1 as a key molecule involved in the regulation of EOC PT-resistance and progression disclosing the possibility that it could be used as a new biomarker of PT-resistance and/or therapeutic target. MDPI 2019-12-18 /pmc/articles/PMC7016675/ /pubmed/31861382 http://dx.doi.org/10.3390/cells9010006 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Sonego, Maura Poletto, Evelina Pivetta, Eliana Nicoloso, Milena S. Pellicani, Rosanna Rampioni Vinciguerra, Gian Luca Citron, Francesca Sorio, Roberto Mongiat, Maurizio Baldassarre, Gustavo TIMP-1 Is Overexpressed and Secreted by Platinum Resistant Epithelial Ovarian Cancer Cells |
title | TIMP-1 Is Overexpressed and Secreted by Platinum Resistant Epithelial Ovarian Cancer Cells |
title_full | TIMP-1 Is Overexpressed and Secreted by Platinum Resistant Epithelial Ovarian Cancer Cells |
title_fullStr | TIMP-1 Is Overexpressed and Secreted by Platinum Resistant Epithelial Ovarian Cancer Cells |
title_full_unstemmed | TIMP-1 Is Overexpressed and Secreted by Platinum Resistant Epithelial Ovarian Cancer Cells |
title_short | TIMP-1 Is Overexpressed and Secreted by Platinum Resistant Epithelial Ovarian Cancer Cells |
title_sort | timp-1 is overexpressed and secreted by platinum resistant epithelial ovarian cancer cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016675/ https://www.ncbi.nlm.nih.gov/pubmed/31861382 http://dx.doi.org/10.3390/cells9010006 |
work_keys_str_mv | AT sonegomaura timp1isoverexpressedandsecretedbyplatinumresistantepithelialovariancancercells AT polettoevelina timp1isoverexpressedandsecretedbyplatinumresistantepithelialovariancancercells AT pivettaeliana timp1isoverexpressedandsecretedbyplatinumresistantepithelialovariancancercells AT nicolosomilenas timp1isoverexpressedandsecretedbyplatinumresistantepithelialovariancancercells AT pellicanirosanna timp1isoverexpressedandsecretedbyplatinumresistantepithelialovariancancercells AT rampionivinciguerragianluca timp1isoverexpressedandsecretedbyplatinumresistantepithelialovariancancercells AT citronfrancesca timp1isoverexpressedandsecretedbyplatinumresistantepithelialovariancancercells AT sorioroberto timp1isoverexpressedandsecretedbyplatinumresistantepithelialovariancancercells AT mongiatmaurizio timp1isoverexpressedandsecretedbyplatinumresistantepithelialovariancancercells AT baldassarregustavo timp1isoverexpressedandsecretedbyplatinumresistantepithelialovariancancercells |