Background/purpose: Rhabdoid tumor of the kidney (RTK) is a lethal malignancy of childhood for which there currently are no effective therapies. Because vascular endothelial growth factor (VEGF) is nearly ubiquitous in human tumors, the authors hypothesized that a xenograft model of RTK would (1) express VEGF and (2) respond to anti-VEGF intervention.
Methods: A total of 2 x 10(6) cultured RTK cells were implanted intrarenally (G-401) in athymic mice. Control/treated animals received either vehicle (phosphate-buffered saline, PBS) or anti-VEGF antibody (anti-VEGF) for 5 weeks (n = 20, 17, respectively). Vasculature was mapped by angiography and immunostaining. Apoptosis was assessed by TdT-mediated dUTP nick end labeling (TUNEL) assay, VEGF expression examined by reverse transcription polymerase chain reaction, and tumor weights compared by Kruskal-Wallis analysis.
Results: Mean tumor weights were not altered significantly by anti-VEGF (0.78-g, controls v 0.56-g treated tumors; P value, not significant). Grossly, xenografts grew in a novel manner, encasing rather than invading the kidney, and did not metastasize. PECAM-1 immunostaining and fluorescein angiography showed similar vascularity in control and treated xenografts. Both apoptosis and VEGF expression were unchanged in treated specimens.
Conclusions: Unexpectedly, growth of RTK xenografts was not inhibited by specific anti-VEGF antibody, although these tumors express significant amounts of VEGF. In addition, RTK vasculature, apoptosis, and VEGF expression were not substantially altered by anti-VEGF antibody. These results suggest that tumor-derived VEGF is of highly variable importance in different malignancies.
Copyright 2002 by W.B. Saunders Company.