Vascular endothelial growth factor: Acting as an autocrine growth factor for human gastric adenocarcinoma cell MGC803

Vascular endothelial growth factor (VEGF) is known to be a highly specific mitogen for endothelial cells through two high-affinity tyrosine kinase rec eptors, VEGFR-1 and VEGFR-2, which are almost specifically expressed in end othelial cells. However, recent findings showed that VEGF receptors may als o expressed by nonendothelial cells, especially by tumor cells. To further understand the functional expression of VEGF receptors by nonendothelial ce lls, our preliminary screening detected the expression of VEGFR-2 in 115 di fferent paraffin-embedded cancer specimens including 35 cases of bladder tu mor, 30 cases of breast cancer, 25 cases of intestinal cancer, and 25 cases of lung cancer with immunohistochemistry. The results showed that VEGFR-2 was widely expressed in different tumor tissues. By reverse transcription P CR, NCI-H23, NCI-H460, MGC803, MDA-MB-231,293, and MCF7 cells were evaluate d for the mRNA expression of both VEGF and VEGFR-2. The data indicated that all these tumor cell lines expressed detectable amounts of VEGF mRNA, but only 293, MCF7, and MGC803 cells coexpressed VEGFR-2. Immunoblot analysis a lso demonstrated the expression of VEGFR-2 at protein level. We further dem onstrate that exogenous rhVEGF(165) could stimulate cell growth in MGC803, a tumor cell line derived from gastric adenocarcinoma, in a dose- and time- dependent manner. Furthermore, the antibodies against rhVEGF(165) and VEGFR -2 could block rhVEGF(165)-mediated proliferation of MGC803 cells. These un expected results provided direct evidence that VEGF may act as an autocrine growth factor to induce the proliferation of gastric adenocarcinoma cells as well as tumor angiogenic cells, thus suggesting a promising tumor therap eutic application based upon the VEGF system. (C) 2001 Academic Press.