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Updated: Jan 1, 2026
Author Spotlight: Unveiling the Role of TMOD3 in Platinum Resistance and Immune Infiltration in Ovarian Cancer
Published on: August 2, 2024
TIMP-1 is Overexpressed and Secreted by Platinum Resistant Epithelial Ovarian Cancer Cells
Maura Sonego1, Evelina Poletto1, Eliana Pivetta1
1Division of Molecular Oncology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081 Aviano, Italy.
Abstract:
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.
Insights
Tissue inhibitor of metalloproteinases 1 (TIMP-1) is upregulated in platinum-resistant ovarian cancer cells. High TIMP-1 levels correlate with decreased survival, suggesting its role in chemoresistance and progression.
Area of Science:
- Gynecologic Oncology
- Cancer Biology
- Translational Research
Background:
- Epithelial ovarian cancer (EOC) is a leading cause of cancer death in women.
- Chemoresistance, particularly to platinum (PT) agents, is a major challenge in EOC treatment.
- Angiogenesis is a validated therapeutic target in EOC.
Purpose of the Study:
- To investigate if EOC cells resistant to platinum (PT) treatment exhibit altered angiogenic potential.
- To identify specific molecular factors involved in PT resistance and angiogenesis in EOC.
Main Methods:
- Proteomic analysis of PT-resistant EOC cell lines (TOV-112D, OVSAHO).
- Assessment of tissue inhibitor of metalloproteinases 1 (TIMP-1) expression and its functional impact.
- Correlation analysis of TIMP-1 levels with patient survival and treatment outcomes (PT, bevacizumab).
Main Results:
- TIMP-1 was identified as the sole upregulated secreted factor in PT-resistant EOC cells.
- TIMP-1 influences both tumor cell response to PT and endothelial cell migration/proliferation.
- Elevated TIMP-1 levels in advanced EOC patients are associated with poorer overall survival, especially with PT or bevacizumab treatment.
Conclusions:
- TIMP-1 is a key regulator of platinum resistance and progression in epithelial ovarian cancer.
- TIMP-1 may serve as a predictive biomarker for PT resistance and a potential therapeutic target.
- Targeting TIMP-1 could offer new strategies to overcome chemoresistance and improve outcomes in EOC.
