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VEGF and VEGFR‐1 are coexpressed by epithelial and stromal cells of renal cell carcinoma
Author(s) -
Rivet Jacqueline,
Mourah Samia,
Murata Hideyuki,
Mounier Nicolas,
Pisonero Helena,
MongiatArtus Pierre,
Teillac Pierre,
Calvo Fabien,
Janin Anne,
Dosquet Christine
Publication year - 2007
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.23186
Subject(s) - vegf receptors , stromal cell , medicine , renal cell carcinoma , cancer research , pathology
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. © 2007 American Cancer Society.