Vascular endothelial growth factor (VEGF) expression regulates angiogenesis accompanying tumor growth in a peritoneal disseminated tumor model.

Quantitative analysis of the process of tumor angiogenesis was performed in a new animal model of tumor microcirculation, in which colon carcinoma cells were inoculated into the peritoneal cavity of rats. Time-dependent changes in the microvascular architecture of mesenteric microvessels of tumor-bearing rats were visualized using an intravital microscope. Simultaneously, the expression of vascular endothelial growth factor (VEGF) by the tumor cells and VEGF secretion into ascites were analyzed. The results showed that VEGF increases microvascular permeability and stimulates the growth of microvessels into the tumor and that the spatial and temporal concentration of VEGF is strongly correlated. Such a correlation was stronger in the early angiogenic stages of tumor growth than in the subsequently occurring multiple metastatic stage, when VEGF was still observed at a high level in tumor surroundings. Thus, VEGF is suggested to be primarily involved in the pathophysiological control of angiogenesis accompanying tumor progression.