Angiotensin II Facilitates Breast Cancer Cell Migration and Metastasis

Angiotensin II Facilitates Breast Cancer Cell Migration and Metastasis

Author Rodrigues-Ferreira, Sylvie Google Scholar
Abdelkarim, Mohamed Google Scholar
Dillenburg-Pilla, Patricia Google Scholar
Luissint, Anny-Claude Google Scholar
di-Tommaso, Anne Google Scholar
Deshayes, Frederique Google Scholar
Pontes, Carmen Lucia S. Google Scholar
Molina, Angie Google Scholar
Cagnard, Nicolas Google Scholar
Letourneur, Franck Google Scholar
Morel, Marina Google Scholar
Reis, Rosana I. Google Scholar
Casarini, Dulce Elena Autor UNIFESP Google Scholar
Terris, Benoit Google Scholar
Couraud, Pierre-Olivier Google Scholar
Costa-Neto, Claudio M. Google Scholar
Di Benedetto, Melanie Google Scholar
Nahmias, Clara Google Scholar
Institution INSERM
Univ Paris 05
Univ Paris 13
Universidade de São Paulo (USP)
Universidade Federal de São Carlos (UFSCar)
Universidade Federal de São Paulo (UNIFESP)
Abstract Breast cancer metastasis is a leading cause of death by malignancy in women worldwide. Efforts are being made to further characterize the rate-limiting steps of cancer metastasis, i.e. extravasation of circulating tumor cells and colonization of secondary organs. in this study, we investigated whether angiotensin II, a major vasoactive peptide both produced locally and released in the bloodstream, may trigger activating signals that contribute to cancer cell extravasation and metastasis. We used an experimental in vivo model of cancer metastasis in which bioluminescent breast tumor cells (D3H2LN) were injected intra-cardiacally into nude mice in order to recapitulate the late and essential steps of metastatic dissemination. Real-time intravital imaging studies revealed that angiotensin II accelerates the formation of metastatic foci at secondary sites. Pre-treatment of cancer cells with the peptide increases the number of mice with metastases, as well as the number and size of metastases per mouse. in vitro, angiotensin II contributes to each sequential step of cancer metastasis by promoting cancer cell adhesion to endothelial cells, trans-endothelial migration and tumor cell migration across extracellular matrix. At the molecular level, a total of 102 genes differentially expressed following angiotensin II pretreatment were identified by comparative DNA microarray. Angiotensin II regulates two groups of connected genes related to its precursor angiotensinogen. Among those, up-regulated MMP2/MMP9 and ICAM1 stand at the crossroad of a network of genes involved in cell adhesion, migration and invasion. Our data suggest that targeting angiotensin II production or action may represent a valuable therapeutic option to prevent metastatic progression of invasive breast tumors.
Language English
Sponsor University Paris Descartes
Centre National de la Recherche Scientifique
Ligue Contre le Cancer-Comite Ile de France
Association pour la Recherche contre le Cancer (ARC)
Fondation RAJA
association Prolific
Date 2012-04-20
Published in Plos One. San Francisco: Public Library Science, v. 7, n. 4, 8 p., 2012.
ISSN 1932-6203 (Sherpa/Romeo, impact factor)
Publisher Public Library Science
Extent 8
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000305339200092

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