CELLS TRANSFECTED WITH THE BASIC FIBROBLAST GROWTH-FACTOR GENE FUSED TO A SIGNAL SEQUENCE ARE INVASIVE IN-VITRO AND IN-SITU IN THE BRAIN

INVASIVENESS IS A critical event in the development of malignancy in b rain tumors. A potential molecular mediator is basic fibroblast growth factor (bFGF). NIH-3T3 cells transfected with the bFGF gene fused wit h a signal peptide sequence (signal peptide bFGF) acquire an invasive phenotype as measured by in vitro assays of invasion including: 1) the formation of branching networks on Matrigel; 2) invasiveness in a che moinvasion assay; 3) migration in a cell spreading assay; 4) detection of an M(r) 92,000 gelatinase; and 5) local invasion into the surround ing neuropil after injection in the athymic mouse brain. By contrast, cells transfected with only the native bFGF gene (wild-type bFGF): 1) formed discrete cell clusters on Matrigel; 2) were less invasive and m igratory in vitro; 3) released minimal M(r) 92,000 collagenase; and 4) in vivo formed a pseudocapsule that separated the tumor cells from th e neuropil. Quantitation of bFGF in the conditioned serum-free medium of the cell lines by enzyme-linked immunosorbent assay demonstrated th at the signal peptide-bFGF cell clone secreted bFGF. These findings su ggest a role for bFGF-mediated pathways and collagenase as molecular d eterminants of invasiveness in the brain.