Cell motility, invasion, and malignancy induced by overexpression of K-FGF or bFGF.
We have tested the hypothesis that fibroblast growth factors contribute to cell locomotion and invasion, by investigating the properties of NIH-3T3 fibroblasts that secrete K-FGF following transfection with the K-fgf proto-oncogene and NIH-3T3 fibroblasts transfected with either the normal basic fibroblast growth factor (bFGF) coding sequence that lacks a known secretory signal sequence, or a chimeric bFGF sequence fused to an immunoglobulin signal sequence that targets the growth factor to the secretory pathway. The cell lines were tested for altered invasive characteristics on a physiologically relevant collagen substratum, and their motility rates were measured in cell locomotion assays using time-lapse video microscopy in the absence or presence of suramin, an inhibitor of growth factor-receptor interaction. The data were analyzed by comparing the motility rates of all K-fgf- and bFGF-transfected cell lines as a function of malignant potential. These studies show for the first time that K-fgf gene expression potently increases cell motility characteristics. Further, the bFGF transfectants generally exhibited increased rates of cell locomotion which were not dependent upon the presence of a signal sequence for secretion. These results support models of cell locomotion in which stimulation of this process can occur through both autocrine and intracrine pathways. In addition, a significant correlation was found to exist between cell locomotion and malignant potential, supporting the view that growth factor-induced motility, although not sufficient on its own to induce metastasis, is important in the promotion of tumor cell dissemination.
Taylor
W R
WR
Manitoba Institute of Cell Biology, University of Manitoba, Winnipeg, Canada.
Greenberg
A H
AH
Turley
E A
EA
Wright
J A
JA
D016475:3T3 Cells / Q000187:drug effects; D000818:Animals; D002465:Cell Movement / Q000187:drug effects*; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000494:pharmacology*; D051519:Fibroblast Growth Factor 4; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000494:pharmacology*; D051379:Mice; D009361:Neoplasm Invasiveness / Q000235:genetics*; D021382:Protein Sorting Signals; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000494:pharmacology*; D011519:Proto-Oncogenes / Q000502:physiology*; D013498:Suramin / Q000494:pharmacology; D014162:Transfection
C496446:Fgf4 protein, mouse; D051519:Fibroblast Growth Factor 4; D021382:Protein Sorting Signals; D011518:Proto-Oncogene Proteins; D016222:Fibroblast Growth Factor 2; D013498:Suramin; D005346:Fibroblast Growth Factors