Circulating Tumor Cells Characterization Revealed TIMP1 as a Potential Therapeutic Target in Ovarian Cancer
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
Affiliations
Manuel Abreu
Liquid Biopsy Analysis Unit, Translational Medical Oncology (Oncomet), Health Research Institute of Santiago (IDIS), 15706 Santiago de Compostela, Spain
Pablo Cabezas-Sainz
Department of Genetics, University of Santiago de Compostela, Campus de Lugo, 27002 Lugo, Spain
Lorena Alonso-Alconada
Nasasbiotech, S.L., Canton Grande 3, 15003 A Coruña, Spain
Alba Ferreirós
Nasasbiotech, S.L., Canton Grande 3, 15003 A Coruña, Spain
Patricia Mondelo-Macía
Liquid Biopsy Analysis Unit, Translational Medical Oncology (Oncomet), Health Research Institute of Santiago (IDIS), 15706 Santiago de Compostela, Spain
Ramón Manuel Lago-Lestón
Liquid Biopsy Analysis Unit, Translational Medical Oncology (Oncomet), Health Research Institute of Santiago (IDIS), 15706 Santiago de Compostela, Spain
Alicia Abalo
Liquid Biopsy Analysis Unit, Translational Medical Oncology (Oncomet), Health Research Institute of Santiago (IDIS), 15706 Santiago de Compostela, Spain
Eva Díaz
Fundación MD Anderson Internacional, C/Gómez Hemans 2, 28033 Madrid, Spain
Sara Palacios-Zambrano
MD Anderson Cancer Center, C/Arturo Soria 270, 28029 Madrid, Spain
Alejandro Rojo-Sebastian
Fundación MD Anderson Internacional, C/Gómez Hemans 2, 28033 Madrid, Spain
Rafael López-López
Translational Medical Oncology (Oncomet), Health Research Institute of Santiago de Compostela (IDIS), Complexo Hospitalario Universitario de Santiago de Compostela (SERGAS), 15706 Santiago de Compostela, Spain
Laura Sánchez
Department of Genetics, University of Santiago de Compostela, Campus de Lugo, 27002 Lugo, Spain
Gema Moreno-Bueno
Fundación MD Anderson Internacional, C/Gómez Hemans 2, 28033 Madrid, Spain
Laura Muinelo-Romay
Liquid Biopsy Analysis Unit, Translational Medical Oncology (Oncomet), Health Research Institute of Santiago (IDIS), 15706 Santiago de Compostela, Spain
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 aim of the present study was the characterization of CTCs from ovarian cancer patients, paying special attention to cell plasticity characteristics to better understand the biology of these cells. 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.
