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 brain tumors. A potential molecular mediator is basic fibroblast growth factor (bFGF). NIH-3T3 cells transfected with the bFGF gene fused with 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 chemoinvasion assay; 3) migration in a cell spreading assay; 4) detection of an Mr 92,000 gelatinase; and 5) local invasion into the surrounding 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 migratory in vitro; 3) released minimal Mr 92,000 collagenase; and 4) in vivo formed a pseudocapsule that separated the tumor cells from the neuropil. Quantitation of bFGF in the conditioned serum-free medium of the cell lines by enzyme-linked immunosorbent assay demonstrated that the signal peptide-bFGF cell clone secreted bFGF. These findings suggest a role for bFGF-mediated pathways and collagenase as molecular determinants of invasiveness in the brain.
Gately
S
S
Division of Neurosurgery, Northwestern University School of Medicine, Chicago, Illinois, USA.
Tsanaclis
A M
AM
Takano
S
S
Klagsbrun
M
M
Brem
S
S
D016475:3T3 Cells; D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics*; D002465:Cell Movement / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D017364:Collagenases / Q000235:genetics; D016222:Fibroblast Growth Factor 2 / Q000235:genetics*; D051379:Mice; D008819:Mice, Nude; D008970:Molecular Weight; D009361:Neoplasm Invasiveness / Q000235:genetics*; D009368:Neoplasm Transplantation; D010641:Phenotype; D021382:Protein Sorting Signals / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000235:genetics*; D014162:Transfection / Q000235:genetics*
D021382:Protein Sorting Signals; D011993:Recombinant Fusion Proteins; D016222:Fibroblast Growth Factor 2; D017364:Collagenases