Fiche publication
Date publication
novembre 2014
Auteurs
Membres identifiés du Cancéropôle Est :
Dr DE ARCANGELIS Adèle
Tous les auteurs :
Bouvard C, Segaoula Z, De Arcangelis A, Galy-Fauroux I, Mauge L, Fischer AM, Georges-Labouesse E, Helley D
Lien Pubmed
Résumé
The alpha6 integrin subunit (alpha6) has been implicated in cancer cell migration and in the progression of several malignancies, but its role in tumor angiogenesis is unclear. In mice, anti-alpha6 blocking antibodies reduce tumor angiogenesis, whereas Tie1-dependent alpha6 gene deletion enhances neovessel formation in melanoma and lung carcinoma. To clarify the discrepancy in these results we used the cre-lox system to generate a mouse line, alpha6fl/flTie2Cre(+), with alpha6 gene deletion specifically in Tie2-lineage cells: endothelial cells, pericytes, subsets of hematopoietic stem cells, and Tie2-expressing monocytes/macrophages (TEMs), known for their proangiogenic properties. Loss of alpha6 expression in alpha6fl/flTie2Cre(+) mice reduced tumor growth in a murine B16F10 melanoma model. Immunohistological analysis of the tumors showed that Tie2-dependent alpha6 gene deletion was associated with reduced tumor vascularization and with reduced infiltration of proangiogenic Tie2-expressing macrophages. These findings demonstrate that alpha6 integrin subunit plays a major role in tumor angiogenesis and TEM infiltration. Targeting alpha6 could be used as a strategy to reduce tumor growth.
Référence
Int J Oncol. 2014 Nov;45(5):2058-64
