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oai:recercat.cat:2445/1548582025-12-05T09:20:40Zcom_2072_1057col_2072_478799col_2072_478916col_2072_478917col_2072_478929

00925njm 22002777a 4500 dc Figueras i Amat, Agnès author Alsina Sanchís, Elisenda author Lahiguera, Álvaro author Abreu, Manuel author Muinelo Romay, Laura author Moreno-Bueno, Gema author Casanovas i Casanovas, Oriol author Graupera i Garcia-Milà, Mariona author Matias-Guiu, Xavier, 1958- author Vidal-Bel, August author Villanueva Garatachea, Alberto author Viñals Canals, Francesc author 2020-04-02T12:09:46Z 2020-04-02T12:09:46Z 2018-02-01 2020-04-02T12:09:46Z Epithelial ovarian cancer is characterized by a low recovery rate because the disease is typically diagnosed at an advanced stage, by which time most patients (80%) already exhibit disseminated neoplasia. The cytokine receptor CXCR4 has been implicated in the development of metastasis in various tumor types. Using a patient-derived tissue macroarray and mRNA expression analysis, we observed high CXCR4 levels in high-grade serous epithelial ovarian carcinomas, the most metastatic tumor, compared with those in endometrioid carcinomas. CXCR4 inhibition by treatment with the CXCR4 antagonist AMD3100 or by expression of shRNA anti-CXCR4 similarly inhibited angiogenesis in several models of ovarian carcinomas orthotopically grown in nude mice, but the effect on tumor growth was correlated with the levels of CXCR4 expression. Moreover, CXCR4 inhibition completely blocked dissemination and metastasis. This effect was associated with reduced levels of active Src, active ERKs, the inhibition of EMT transition, and block of hematogenous ovarian cancer dissemination decreasing circulating human tumoral cells (CTC). In tumors, CXCR4-expressing cells also had more mesenchymal characteristics. In conclusion, our results indicate that CXCR4 expression confers a proinvasive phenotype to ovarian carcinoma cells. Thus, anti-CXCR4 therapy is a possible agent for a complementary treatment of advanced disseminated epithelial high-grade serous ovarian cancer patients. Cèl·lules epitelials Càncer d'ovari Metàstasi Epithelial cells Ovarian cancer Metastasis A role for CXCR4 in peritoneal and hematogenous ovarian cancer dissemination