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Title: A role for CXCR4 in peritoneal and hematogenous ovarian cancer dissemination
Author: Figueras i Amat, Agnès
Alsina Sanchís, Elisenda
Lahiguera, Álvaro
Abreu, Manuel
Muinelo Romay, Laura
Moreno-Bueno, Gema
Casanovas i Casanovas, Oriol
Graupera i Garcia-Milà, Mariona
Matias-Guiu, Xavier
Vidal-Bel, August
Villanueva Garatachea, Alberto
Viñals Canals, Francesc
Keywords: Cèl·lules epitelials
Càncer d'ovari
Epithelial cells
Ovarian cancer
Issue Date: 1-Feb-2018
Publisher: American Association for Cancer Research
Abstract: 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.
Note: Versió postprint del document publicat a:
It is part of: Molecular Cancer Therapeutics, 2018, vol. 17, num. 2, p. 532-543
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ISSN: 1535-7163
Appears in Collections:Articles publicats en revistes (Ciències Fisiològiques)
Articles publicats en revistes (Patologia i Terapèutica Experimental)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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