Expression of angiogenic factors, basic fibroblast growth factor and vascular endothelial growth factor, in human biliary tract carcinoma cell lines.

In order to clarify angiogenic mechanism in biliary tract carcinoma, expressions and functions of basic fibroblast growth factor (bFGF) and its receptors (FGFR-1-4), and vascular endothelial growth factor (VEGF) and its receptors were investigated by using human biliary tract carcinoma cell lines (KMC-1, KMC-2, KMBC and KMG-C). Expression of bFGF was confirmed in KMC-1 and KMC-2, and that of FGFR-1-4 in all the cell lines except no FGFR-2 in KMC-2. Expression of VEGF was detected in all the cell lines, whereas the cell lines did not express VEGF receptors. Addition of anti-bFGF neutralizing antibody to the medium did not suppress cell proliferation, whereas exogenous bFGF with or without heparin accelerated cell proliferation in all cell lines. Addition of anti-bFGF neutralizing antibody or anti-VEGF neutralizing antibody to the co-culture of human umbilical vascular endothelial cells (HUVEC) and KMC-2 suppressed the proliferation of HUVEC. Surgically obtained cholangiocarcinoma tissues (n=7) were immunohistochemically negative to bFGF, while six of the seven were positive to VEGF. These findings suggested that human biliary tract carcinoma cells express both bFGF and VEGF not as autocrine growth factors but as angiogenic factors. On the other hand, expression of VEGF was found at a higher frequency than bFGF both in the cell lines and tissues.