Circulating Tumor Cells Characterization Revealed TIMP1 as a Potential Therapeutic Target in Ovarian Cancer

循环肿瘤细胞表征显示 TIMP1 是卵巢癌的潜在治疗靶点

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作者:Manuel Abreu, Pablo Cabezas-Sainz, Lorena Alonso-Alconada, Alba Ferreirós, Patricia Mondelo-Macía, Ramón Manuel Lago-Lestón, Alicia Abalo, Eva Díaz, Sara Palacios-Zambrano, Alejandro Rojo-Sebastian, Rafael López-López, Laura Sánchez, Gema Moreno-Bueno, Laura Muinelo-Romay

Background

Recent studies showed a relevant role of hematogenous spread in ovarian cancer and the interest of circulating tumor cells (CTCs) monitoring as a prognosis marker. The

Conclusions

Overall, we evidenced the utility of the molecular characterization of EpCAM+ CTCs from advanced ovarian cancer patients to identify biomarkers with potential applicability for disseminated disease detection and as therapeutic targets such as TIMP1.

Methods

CTCs isolation was carried out in 38 patients with advanced high-grade serous ovarian cancer using in parallel CellSearch and an alternative EpCAM-based immunoisolation followed by RT-qPCR analysis to characterize these cells.

Results

Epithelial CTCs were found in 21% of patients, being their presence higher in patients with extraperitoneal metastasis. Importantly, this population was characterized by the expression of epithelial markers as MUC1 and CK19, but also by genes associated with mesenchymal and more malignant features as TIMP1, CXCR4 and the stem markers CD24 and CD44. In addition, we evidenced the relevance of TIMP1 expression to promote tumor proliferation, suggesting its interest as a therapeutic target. Conclusions: Overall, we evidenced the utility of the molecular characterization of EpCAM+ CTCs from advanced ovarian cancer patients to identify biomarkers with potential applicability for disseminated disease detection and as therapeutic targets such as TIMP1.

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