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Open AccessArticle

TIMP-1 Is Overexpressed and Secreted by Platinum Resistant Epithelial Ovarian Cancer Cells

1
Division of Molecular Oncology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081 Aviano, Italy
2
Deparment of Medical Oncology Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081 Aviano, Italy
*
Authors to whom correspondence should be addressed.
Contributed equally to this work as first authors.
Contributed equally to this work as senior authors.
Received: 30 October 2019 / Revised: 9 December 2019 / Accepted: 12 December 2019 / Published: 18 December 2019
(This article belongs to the Special Issue Molecular and Cellular Mechanisms of Cancers: Ovarian Cancer)
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. View Full-Text
Keywords: epithelial ovarian cancer; platinum resistance; angiogenesis epithelial ovarian cancer; platinum resistance; angiogenesis
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Sonego, M.; Poletto, E.; Pivetta, E.; Nicoloso, M.S.; Pellicani, R.; Rampioni Vinciguerra, G.L.; Citron, F.; Sorio, R.; Mongiat, M.; Baldassarre, G. TIMP-1 Is Overexpressed and Secreted by Platinum Resistant Epithelial Ovarian Cancer Cells. Cells 2020, 9, 6.

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