A role for CXCR4 in peritoneal and hematogenous ovarian cancer dissemination

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 tum...

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Autores: 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, 1958-, Vidal-Bel, August, Villanueva Garatachea, Alberto, Viñals Canals, Francesc
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2018
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/154858
Acceso en línea:https://hdl.handle.net/2445/154858
Access Level:acceso abierto
Palabra clave:Cèl·lules epitelials
Càncer d'ovari
Metàstasi
Epithelial cells
Ovarian cancer
Metastasis
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spelling A role for CXCR4 in peritoneal and hematogenous ovarian cancer disseminationFigueras i Amat, AgnèsAlsina Sanchís, ElisendaLahiguera, ÁlvaroAbreu, ManuelMuinelo Romay, LauraMoreno-Bueno, GemaCasanovas i Casanovas, OriolGraupera i Garcia-Milà, MarionaMatias-Guiu, Xavier, 1958-Vidal-Bel, AugustVillanueva Garatachea, AlbertoViñals Canals, FrancescCèl·lules epitelialsCàncer d'ovariMetàstasiEpithelial cellsOvarian cancerMetastasisEpithelial 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.American Association for Cancer Research2018info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfhttps://hdl.handle.net/2445/154858Articles publicats en revistes (Ciències Fisiològiques)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésVersió postprint del document publicat a: https://doi.org/10.1158/1535-7163.MCT-17-0643Molecular Cancer Therapeutics, 2018, vol. 17, num. 2, p. 532-543https://doi.org/10.1158/1535-7163.MCT-17-0643(c) American Association for Cancer Research, 2018info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1548582026-05-27T06:46:51Z
dc.title.none.fl_str_mv A role for CXCR4 in peritoneal and hematogenous ovarian cancer dissemination
title A role for CXCR4 in peritoneal and hematogenous ovarian cancer dissemination
spellingShingle A role for CXCR4 in peritoneal and hematogenous ovarian cancer dissemination
Figueras i Amat, Agnès
Cèl·lules epitelials
Càncer d'ovari
Metàstasi
Epithelial cells
Ovarian cancer
Metastasis
title_short A role for CXCR4 in peritoneal and hematogenous ovarian cancer dissemination
title_full A role for CXCR4 in peritoneal and hematogenous ovarian cancer dissemination
title_fullStr A role for CXCR4 in peritoneal and hematogenous ovarian cancer dissemination
title_full_unstemmed A role for CXCR4 in peritoneal and hematogenous ovarian cancer dissemination
title_sort A role for CXCR4 in peritoneal and hematogenous ovarian cancer dissemination
dc.creator.none.fl_str_mv 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, 1958-
Vidal-Bel, August
Villanueva Garatachea, Alberto
Viñals Canals, Francesc
author Figueras i Amat, Agnès
author_facet 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, 1958-
Vidal-Bel, August
Villanueva Garatachea, Alberto
Viñals Canals, Francesc
author_role author
author2 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, 1958-
Vidal-Bel, August
Villanueva Garatachea, Alberto
Viñals Canals, Francesc
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Cèl·lules epitelials
Càncer d'ovari
Metàstasi
Epithelial cells
Ovarian cancer
Metastasis
topic Cèl·lules epitelials
Càncer d'ovari
Metàstasi
Epithelial cells
Ovarian cancer
Metastasis
description 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.
publishDate 2018
dc.date.none.fl_str_mv 2018
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/154858
url https://hdl.handle.net/2445/154858
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Versió postprint del document publicat a: https://doi.org/10.1158/1535-7163.MCT-17-0643
Molecular Cancer Therapeutics, 2018, vol. 17, num. 2, p. 532-543
https://doi.org/10.1158/1535-7163.MCT-17-0643
dc.rights.none.fl_str_mv (c) American Association for Cancer Research, 2018
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) American Association for Cancer Research, 2018
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv American Association for Cancer Research
publisher.none.fl_str_mv American Association for Cancer Research
dc.source.none.fl_str_mv Articles publicats en revistes (Ciències Fisiològiques)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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