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Background  Tumor endothelial transdifferentiation and VEGFR1/2 expression by cancer cells have been reported in glioblastoma but remain poorly documented for many other cancer types.    Methods  To characterize vasculature of patient-derived tumor xenografts (PDXs), largely used in preclinical anti-angiogenic assays, we designed here species-specific real-time quantitative RT-PCR assays. Human and mouse  PECAM1/CD31, ENG/CD105, FLT1/VEGFR1, KDR / VEGFR2  and  VEGFA  transcripts were analyzed in a large series of 150 PDXs established from 8 different tumor types (53 colorectal, 14 ovarian, 39 breast and 15 renal cell cancers, 6 small cell and 5 non small cell lung carcinomas, 13 cutaneous melanomas and 5 glioblastomas) and in two bevacizumab-treated non small cell lung carcinomas xenografts.    Results  As expected, mouse cell proportion in PDXs -evaluated by quantifying expression of the housekeeping gene  TBP-  correlated with all mouse endothelial markers and human  VEGFA  RNA levels. More interestingly, we observed human  PECAM1/CD31 and ENG/CD105  expression in all tumor types, with higher rate in glioblastoma and renal cancer xenografts. Human  VEGFR  expression profile varied widely depending on tumor types with particularly high levels of human  FLT1 / VEGFR1  transcripts in colon cancers and non small cell lung carcinomas, and upper levels of human  KDR / VEGFR2  transcripts in non small cell lung carcinomas. Bevacizumab treatment induced significant low expression of mouse  Pecam1/Cd31, Eng/Cd105 ,  Flt1 / Vegfr1  and  Kdr / Vefr2  while the human  PECAM1/CD31  and  VEGFA  were upregulated.    Conclusions  Taken together, our results strongly suggest existence of human tumor endothelial cells in all tumor types tested and of both stromal and tumoral autocrine VEGFA-VEGFR1/2 signalings. These findings should be considered when evaluating molecular mechanisms of preclinical response and resistance to tumor anti-angiogenic strategies.

bmc cancer

Vasculature analysis of patient derived tumor xenografts using species-specific PCR assays: evidence of tumor endothelial cells and atypical VEGFA-VEGFR1/2 signalings