EXPRESSION AND GROWTH-STIMULATORY EFFECT OF FIBROBLAST-GROWTH-FACTOR-9 IN HUMAN BRAIN-TUMORS

OBJECTIVE: Fibroblast growth factor 9 (FCF-9) is a relatively new memb er of the FGF family isolated from the conditioned medium of a human g lioblastoma cell line as a secreting type factor that exhibits a growt h-stimulating effect on primary glial cells. To elucidate the roles of FGF-9 in human brain tumors, the expression and biological activities of FCF-9 were studied using culture cells and surgically obtained tum or specimens. METHODS: Measurement of FGF-9 and basic FGF in condition ed media of cell cultures was performed by.using a sandwich enzyme imm unoassay. The mitogenic effect of FCF-9 was evaluated by cell growth s tudies. FCF-9 expression in vivo was demonstrated by immunohistochemis try. RESULTS: One of 4 glioma cell lines and 4 of 16 human meningiomas examined actually secreted detectable amounts of FGF-9 proteins. In c omparison, basic FGF production was detected from 3 of 4 glioma cell l ines and 11 of 16 human meningiomas. Similarly to basic FGF, recombina nt human FGF-9 significantly stimulated the in vitro cell proliferatio n in three of four glioma cell lines investigated in a dose-dependent manner. A time course growth study using U87 MC cells revealed an acce lerated growth stimulation by FCF-9 after Day 4. The growth stimulator y activity was also shown in three of four human meningiomas studied. Moderate to strong immunoreactivity for FCF-9 was observed in 40 (82%) of 49 human brain tumors examined irrespective of origin, tumor type, grade of malignancy, or whether initial or recurrent. In contrast, st rong immunostaining was localized in neurons in the normal human cereb ral cortex. CONCLUSION: The present findings suggest that FCF-9 may be involved in the biology of human brain tumors with a possible importa nce in tumor cell growth. Whether the growth factor is more generally involved in oncogenesis of human tumors awaits further investigation.