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 approximately 4. All six cell lines expressed the proteins and mRNAs of bFGF and FGFR-1, and at least one of FGFR-2 approximately 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 microg/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, hepatocellular carcinoma (HCC) cells may possess a proliferation mechanism regulated by an autocrine mechanism, a paracrine mechanism, or both, which are mediated by bFGF/FGFR.
Ogasawara
S
S
First Department of Pathology, Kurume University School of Medicine, Kurume 830, Japan.
Yano
H
H
Iemura
A
A
Hisaka
T
T
Kojiro
M
M
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis* / Q000494:pharmacology; D015870:Gene Expression; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor / Q000096:biosynthesis*; D014158:Transcription, Genetic; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000906:Antibodies; D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; D016222:Fibroblast Growth Factor 2; C496349:Fgfr1 protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1