VEGF-C/VEGFRS and Cancer Metastasis

Vascular endothelial growth factor C (VEGF-C) is the only factor known causing lymphangiogenesis. We report herein the review of recent experimental studies on VEGF family and their receptors and the molecular mechanisms of the lymphangiogenesis in cancer. According to our study, VEGF-C is a potent stimulator in not only the angiogenesis but also the lymphangiogenesis on the chick chorioallantoic membrane. In the clinical specimens from gastric cancer, there is an intimate relationship between the VEGF receptor-3/VEGF-C tissue status and lymphagiogenesis. RT-PCR and immunohistological examinations demonstrated that VEGF-C was mainly produced from cancer cells and that VEGFR-3 expression was restricted in the endothelial cells of lymphatic vessels. VEGF-C and VEGFR-3 mRNA expression were positively correlated in primary gastric cancers and the number of VEGFR-3 positive lymphatic vessels in VEGF-C mRNA positive tumour was significantly larger than that in VEGF-C negative tumours. The number of such vessels in tumour stroma was closely related to the grade of lymphatic invasion of gastric cancer. Accordingly, we conclude that VEGF-C may induce the lymphatic neogenesis in the stroma of primary gastric cancer. In these circumstances, cancer cells can easily intravasate into the lymphatic vessels, because of the increase of the contact point of cancer cells with lymphatic vessels.