Tumor microenvironment modifications induced by soluble VEGF receptor expression in a rat liver metastasis model. - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Cancer Letters Année : 2010

Tumor microenvironment modifications induced by soluble VEGF receptor expression in a rat liver metastasis model.

Résumé

Vascular endothelial growth factor is a potent pro-angiogenic growth factor which is also known to alter tumor microenvironment by inhibiting dendritic cell differentiation and promoting accumulation of myeloid-derived suppressor cells. In the present study, we analyzed the modifications induced by intratumoral expression of sFLT-1, a soluble VEGF receptor, in a rat metastatic colon carcinoma model. We generated colon cancer cell lines stably expressing sFLT-1 or a mock construct. Human umbilical vein endothelial cells cultured with conditioned medium from sFLT-1-expressing tumor cells exhibit a significantly decreased survival, demonstrating the functionality of the secreted sFLT-1. Invivo, sFLT-1 expression induced a 30% decrease in microvessel density in 15-day old experimental liver metastasis from colon carcinoma. Tumor growth was inhibited by 63% and 52% in left and right liver lobes respectively within 25days. In these tumors, sFLT-1 expression was associated with a decreased myeloid cell infiltration and a modification in the expression of several cytokines/chemokines. Altogether, these results suggest that VEGF trapping by sFLT-1 intratumoral expression results in reduced vascularization, tumor growth inhibition and modification of immune tumor microenvironment.

Dates et versions

hal-00517722 , version 1 (15-09-2010)

Identifiants

Citer

Samuel Bertin, Tala Mohsen-Kanson, Patrick Baqué, Adolfo Gavelli, David Momier, et al.. Tumor microenvironment modifications induced by soluble VEGF receptor expression in a rat liver metastasis model.. Cancer Letters, 2010, epub ahead of print. ⟨10.1016/j.canlet.2010.07.017⟩. ⟨hal-00517722⟩
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