orectal Cancer

The VEGF family is a group of growth factors that regulate the growth of endothelial cells (1,2). So far, at least six members of the VEGF family have been iden-tified, including the VEGF-A/vascular permeability factor (VPF)(3), placenta growth factor (PIGF)(4), VEGF-B/VEGF-related factor (VRF)(5), VEGF-C/VEGF-related protein (VRP)(1,6), VEGF-D/c-fos-induced growth factor /FIGF (7), and VEGF-E (8). The founding member, VEGF-A, plays essential roles in angiogenesis, which is the formation of new blood vessels from vascular endothelia and is known to play an important role in the development, growth, and metastasis of carcinomas in mammals (2). A wide variety of studies strongly suggest that VEGF-A con-tributes to most of the pathologic angiogeneses associ-ated with solid tumors. It is also important to consider the possible impact of lymphangiogenesis (the development of lymphatic vessels) on cancer growth and metastasis. In fact, among colorectal cancer patients, lymph node metasta-sis is an important prognostic factor (9,10,11). The 5-year survival rate of colorectal cancer patients with lymph node metastasis is poorer than that of those without lymph node metastasis (12). VEGF-C is a ligand for VEGFR-2 and VEGFR-3. In adult tissues, VEGFR-2 localizes predominantly to blood vascular endothelial cells, whereas VEGFR-3 is expressed mainly in lymphatic endothelia. Several studies have reported that VEGF-C, together with its major receptor VEGFR-3, may act in a paracrine fash-ion to regulate lymphangiogenesis (13,14,15,16). Because VEGF-C and VEGF-D have the most closely related VEGF homology domains and bind the same receptors (VEGFR-2 and VEGFR-3), these tw