Expressions of basic fibroblast growth factor and its receptors and their relationship to proliferation of human hepatocellular carcinoma cell lines

On six human hepatocellular carcinoma (HCC) cell Lines (KIM-1, KYN-1, KYN-2, KYN-3, HAK-1A, and HAK-1B), we examined expressions and functions of the proteins and messenger RNAs (mRNAs) of basic fibroblast growth factor (bFGF) and its receptor, i.e., fibroblast growth factor receptor-1 (FGFR-1), as well as mRNA expressions of FGFR-2 similar to 4. All six cell lines expressed the proteins and mRNAs of bFGF and FGFR-1, and at least one of FGFR-2 similar to 4 mRNAs. Two of the six cell lines (KYN-1 and KYN-3) presented significant release of bFGF in culture supernatant, while the release in the remaining four cell lines was quite small. Addition of anti-bFGF neutralizing antibody (1, 10, or 20 mu g/mL) to culture medium resulted in marked suppression of cell proliferation in all cell lines except HAK-1A. On the other hand, addition of exogenous bFGF (0.1, 1, or 5 ng/mL) to culture medium stimulated cell proliferation except in KIM-1 and KYN-2. When KIM-1 was transplanted to nude mice and anti-bFGF antibody was injected subcutaneously to a space surrounding the developed tumor, tumor proliferation was significantly suppressed in nude mice that received anti-bFGF antibody than in control mice, but there were no histological differences between the groups, including blood space formation in the stroma. In conclusion, hepatocellullar carcinoma (HCC) cells may possess a proliferation mechanism regulated by an autocrine mechanism, a paracrine mechanism, or both, which are mediated by bFGE/FGFR.