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

被引：10

作者：

Bertin, Samuel ^{[2
]}

Mohsen-Kanson, Tala ^{[2
]}

Baque, Patrick ^{[2
,3
]}

Gavelli, Adolfo ^{[2
]}

Momier, David ^{[1
]}

Anjuere, Fabienne ^{[4
]}

Carle, Georges F. ^{[1
]}

Pierrefite-Carle, Valerie ^{[1
,2
]}

机构：

[1] UNSA, Fac Med, CNRS, UMR 6235,GePITOS, F-06107 Nice 2, France

[2] UNSA, Fac Med, INSERM, U638, F-06107 Nice 2, France

[3] Hop St Roche, Serv Chirurg Urgence, F-06107 Nice, France

[4] UNSA, Fac Med, INSERM, U634, F-06107 Nice 2, France

来源：

CANCER LETTERS | 2010年 / 298卷 / 02期

关键词：

VEGF; Myeloid cells; Liver metastasis; Colon carcinoma; ENDOTHELIAL GROWTH-FACTOR; IMMATURE MYELOID CELLS; SUPPRESSOR-CELLS; TYROSINE KINASE; GENE-THERAPY; PROGRESSION; CANCER; MACROPHAGES; IDENTIFICATION; INHIBITION;

D O I：

10.1016/j.canlet.2010.07.017

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 In vivo 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 25 days 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 (C) 2010 Elsevier Ireland Ltd All rights reserved

引用

页码：264 / 272

页数：9

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