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

Autor: Abreu M; Liquid Biopsy Analysis Unit, Translational Medical Oncology (Oncomet), Health Research Institute of Santiago (IDIS), 15706 Santiago de Compostela, Spain., Cabezas-Sainz P; Department of Genetics, University of Santiago de Compostela, Campus de Lugo, 27002 Lugo, Spain., Alonso-Alconada L; Nasasbiotech, S.L., Canton Grande 3, 15003 A Coruña, Spain., Ferreirós A; Nasasbiotech, S.L., Canton Grande 3, 15003 A Coruña, Spain., Mondelo-Macía P; Liquid Biopsy Analysis Unit, Translational Medical Oncology (Oncomet), Health Research Institute of Santiago (IDIS), 15706 Santiago de Compostela, Spain., Lago-Lestón RM; Liquid Biopsy Analysis Unit, Translational Medical Oncology (Oncomet), Health Research Institute of Santiago (IDIS), 15706 Santiago de Compostela, Spain., Abalo A; Liquid Biopsy Analysis Unit, Translational Medical Oncology (Oncomet), Health Research Institute of Santiago (IDIS), 15706 Santiago de Compostela, Spain., Díaz E; Fundación MD Anderson Internacional, C/Gómez Hemans 2, 28033 Madrid, Spain., Palacios-Zambrano S; MD Anderson Cancer Center, C/Arturo Soria 270, 28029 Madrid, Spain., Rojo-Sebastian A; Fundación MD Anderson Internacional, C/Gómez Hemans 2, 28033 Madrid, Spain., López-López R; 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.; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Monforte de Lemos 3-5, 28029 Madrid, Spain., Sánchez L; Department of Genetics, University of Santiago de Compostela, Campus de Lugo, 27002 Lugo, Spain., Moreno-Bueno G; Fundación MD Anderson Internacional, C/Gómez Hemans 2, 28033 Madrid, Spain.; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Monforte de Lemos 3-5, 28029 Madrid, Spain.; Departamento de Bioquímica, Universidad Autónoma de Madrid (UAM), Instituto de Investigaciones Biomédicas 'Alberto Sols' (CSIC-UAM), IdiPaz, Arzobispo Morcillo 4, 28029 Madrid, Spain., Muinelo-Romay L; Liquid Biopsy Analysis Unit, Translational Medical Oncology (Oncomet), Health Research Institute of Santiago (IDIS), 15706 Santiago de Compostela, Spain.; Departamento de Bioquímica, Universidad Autónoma de Madrid (UAM), Instituto de Investigaciones Biomédicas 'Alberto Sols' (CSIC-UAM), IdiPaz, Arzobispo Morcillo 4, 28029 Madrid, Spain.
Jazyk: angličtina
Zdroj: Cells [Cells] 2020 May 14; Vol. 9 (5). Date of Electronic Publication: 2020 May 14.
DOI: 10.3390/cells9051218
Abstrakt: 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.
Databáze: MEDLINE
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