Overexpression of lymphangiogenic growth factor VEGF-C in human pancreaticcancer

Vascular endothelial growth factor C (VEGF-C) is a lymphangiogenic polypept ide that has been implicated in cancer growth. In this study, we characteri zed VEGF-C expression in cultured human pancreatic cancer cell lines and de termined whether the presence of VEGF-C in human pancreatic cancers is asso ciated with clinicopathologic characteristics. VEGF-C mRNA transcripts were present in all five tested cell lines (Capan-1. MIA-PaCa-2, PANC-1, COLO-3 57, and T3M4). Immunoblotting with a highly specific anti-VEGF-C antibody r evealed the presence of VEGF-C protein in all the cell lines. Northern blot analysis of total RNA revealed an approximately 2.2-fold increase in VEGF- C mRNA transcript in the cancer samples compared with the normal pancreas. Immunohistochemical analysis confirmed the expression of VEGF-C and its rec eptor flt-4 in the cancer cells within the tumor mass. Immunohistochemical analysis of 51 pancreatic cancer tissues revealed the presence of strong VE GF-C immunoreactivity in the cancer cells in 80.4% of the cancer tissues. T he presence of VEGF-C in these cells was associated with increased lymphati c vessels invasion and lymph node metastasis, but not with decreased patien t survival. These findings indicate that VEGF-C and its receptor are common ly overexpressed in human pancreatic cancers and that this factor may contr ibute to the lymphangiogenic process and metastasis in this disorder.