Altered responsiveness of metastatic versus non-metastatic fibroblasts to heparin-binding growth factors.
Cells may become more metastatic partially by gaining growth factor autonomy. This hypothesis was examined by investigating the effects on DNA synthesis of a novel hepatic heparin-binding growth factor (HBGF), and of the well-characterized HBGF, basic fibroblast growth factor (bFGF), using cells of varying metastatic potential. Cells were rendered metastatic by transfection of parental 10T 1/2 fibroblasts with the T24-H-ras oncogene. Both HBGFs stimulated DNA synthesis 2.0-11.1 fold in 10T 1/2 cells in the presence of alpha-minimal essential medium containing 10% fetal bovine serum. In contrast, cells of intermediate metastatic potential or of high metastatic potential, were inhibited approximately 2-fold by the hepatic HBGF, and did not respond to bFGF in alpha-minimal essential medium plus 10% fetal bovine serum. This lack of stimulation was converted to an enhancement of DNA synthesis in the absence of serum when using metastatic but not non-metastatic cells. This is the first demonstration that metastatic cells have a significantly altered responsiveness to these growth factors as compared to non-metastatic parental cells, and indicates that these modifications may play a role in a mechanism of tumor progression.
Schwarz
L C
LC
Manitoba Institute of Cell Biology, Winnipeg, Canada.
Damen
J E
JE
Greenberg
A H
AH
Wright
J A
JA
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D005347:Fibroblasts; D006133:Growth Substances / Q000378:metabolism / Q000494:pharmacology*; D006493:Heparin / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D009362:Neoplasm Metastasis; D009374:Neoplasms, Experimental / Q000473:pathology*; D014407:Tumor Cells, Cultured / Q000473:pathology*
D006133:Growth Substances; D005346:Fibroblast Growth Factors; D006493:Heparin; D004247:DNA