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VEGF and VEGFR-1 are coexpressed by epithelial and stromal cells of renal cell carcinoma.: VEGF and its receptors in renal cell carcinoma

Abstract : BACKGROUND.: Tumor angiogenesis is a dynamic process that plays a major role in cancer progression. Vascular endothelial growth factor (VEGF) and its receptors play a pivotal role in angiogenesis. The expression of VEGF and its receptors VEGFR-1 and VEGFR-2 in renal cell carcinoma (RCC) was investigated in the perspective of anti-VEGF treatments. METHODS.: Total VEGF protein levels were quantified by enzyme-linked immunosorbent assay (ELISA) in tumor tissue samples from surgical specimens of 65 patients with clear cell RCC. At the cellular level the VEGF isoforms VEGFR-1 and VEGFR-2 mRNA were quantified by real-time quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) in laser-microdissected tumoral epithelial as stromal cells and in corresponding normal tissue compartments. Colocalization of VEGF and VEGFR-1 proteins was studied by triple immunofluorescent labeling. RESULTS.: Protein VEGF in cytosolic extracts was significantly higher in tumoral than in nontumoral tissue (P < .0001). Event-free survival was significantly longer for patients with cytosolic VEGF lower than the cutoff (75th percentile of VEGF protein levels, P = .02). In laser-microdissected epithelial cells, VEGF(121) and VEGFR-1 mRNA expressions were higher in RCC than in corresponding nontumoral kidney (P = .007 and P = .002, respectively); they were also higher in stromal cells of RCC compared with nontumoral kidney (P = .02 and P = .003, respectively). There was no differential VEGFR-2 expression in epithelial or in stromal cells of tumoral or nontumoral kidney. By immunofluorescent labeling VEGF and VEGFR-1 colocalized on RCC tumor epithelial and stromal cells. CONCLUSIONS.: Combined laser microdissection and quantitative RT-PCR, as triple immunofluorescent labeling, underlined the preferential expression of the most soluble VEGF isoform, VEGF(121), and its receptor VEGFR-1, but not VEGFR-2, in epithelial and stromal cells of RCC. Cancer 2008. (c) 2007 American Cancer Society.
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Jacqueline Rivet, Samia Mourah, Hideyuki Murata, Nicolas Mounier, Helena Pisonero, et al.. VEGF and VEGFR-1 are coexpressed by epithelial and stromal cells of renal cell carcinoma.: VEGF and its receptors in renal cell carcinoma. Cancer / Cancer (Phila), 2008, 112 (2), pp.433-42. ⟨10.1002/cncr.23186⟩. ⟨inserm-00172271⟩



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