title: Tumor microenvironment modifications induced by soluble VEGF receptor expression in a rat liver metastasis model.
abstract: 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.
authors.affiliation: Université de Nice-Sophia Antipolis, Faculté de Médecine, 06107 Nice cédex 2, France.
authors.forename: Samuel
authors.initials: S
authors.lastname: Bertin
authors.forename: Tala
authors.initials: T
authors.lastname: Mohsen-Kanson
authors.forename: Patrick
authors.initials: P
authors.lastname: Baqué
authors.forename: Adolfo
authors.initials: A
authors.lastname: Gavelli
authors.forename: David
authors.initials: D
authors.lastname: Momier
authors.forename: Fabienne
authors.initials: F
authors.lastname: Anjuere
authors.forename: Georges F
authors.initials: GF
authors.lastname: Carle
authors.forename: Valérie
authors.initials: V
authors.lastname: Pierrefite-Carle
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000556:secondary; D008297:Male; D051379:Mice; D022423:Myeloid Cells / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D014162:Transfection; D047368:Tumor Burden; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D018925:Chemokines; D017077:Culture Media, Conditioned; D016207:Cytokines; D040281:Vascular Endothelial Growth Factor Receptor-1