Anti-angiogene Gentherapie mittels eines dominant negativen VEGF-R2 kodierendem Retroviruses

Abstract

Neoangiogenesis is a mandatory requirement for growth of solid tumors. As of today, the system of VEGF and its receptors VEGF-RI and -RII appears to be the most important one in this process. In the present study we analyzed the role of VEGF and its receptors in growth of pancreatic cancer (PaCa). We analyzed expression of VEGF and both receptors -RI and -RII in human specimens and further elucidated the effect of therapeutic inhibition of VEGF signaling utilizing a dominant negative VEGF-RII mutant retrovirus. VEGF and its receptors were found to be abundantly expressed in human specimens. All cell lines tested expressed both the ligand and its receptors. Therapeutic inhibition of VEGF signaling in vivo markedly reduced tumorigenicity of pancreatic cancer xenografts, when compared to the control group which received wild-type VEGF-RII coding retroviruses. This effect was most likely caused by inhibition of tumor neoangiogenesis, since xenografts of the dominant negative group had a significantly lower microvessel density. This study confirms the important role of tumor neoangiogenesis and further suggests that antiangiogenic therapy may be of immediate value for patients with pancreatic cancer.