VEGF-RII nicht aber VEGF-RI Expression korreliert mit Tumordifferenzierung, Angiogenese und Tumorzell-Wachstum beim Pankreaskazinom

Abstract

Vascular endothelial growth factor (VEGF) and its receptors are key regulators of tumor neoangiogenesis. VEGF is overexpressed in human pancreatic cancer (PaCa), its receptors, however, were thought to be expressed by endothelial cells only. In the present study we further investigated expression of VEGF-RI and -RII in human pancreatic cancer and evaluated cancer cell proliferation during antisense oligonucleotide treatment against both VEGF receptors. The majority of cancer specimens expressed VEGF-RI and VEGF-RII mRNA. Both receptors were found in blood vessels as well as in cancer cells. The presence of VEGF-RII correlated with poor tumor differentiation. Pancreatic cancer cell lines increased DNA synthesis upon VEGF stimulation, which was inhibited by antisense oligonucleotides against VEGF-RII, but not by those against VEGF-RI. Therefore VEGF represents an autocrine growth factor in human pancreatic cancer. VEGF-RII appears to be a key protein in angiogenesis and mitogenesis and its blockade offers a new therapeutic target.