The Int-2/Fgf-3 oncogene product is secreted and associates with extracellular matrix: implications for cell transformation.
NIH3T3 cells transformed by mouse Int-2/Fgf-3 cDNA express a series of Int-2-related products representing discrete stages of processing and glycosylation. We confirm that in at least two highly transformed clonal lines, Int-2 products acquire further modifications and are efficiently secreted into the culture medium. Secreted proteins become associated with the cell surface and extracellular matrix and can be displaced by addition of soluble glycosaminoglycans, specifically heparin, heparan sulfate, and dermatan sulfate. Increasing concentrations of heparin not only compete for Int-2 binding in a dose-dependent manner but also inhibit the growth of these cells and revert the transformed phenotype. These findings reaffirm the notion that extracellular or surface-bound Int-2 protein is instrumental in the morphological transformation of these cells.
Kiefer
P
P
Imperial Cancer Research Fund Laboratories, London, United Kingdom.
Peters
G
G
Dickson
C
C
D016475:3T3 Cells; D000818:Animals; D002471:Cell Transformation, Neoplastic; D003470:Culture Media; D005109:Extracellular Matrix / Q000378:metabolism*; D051518:Fibroblast Growth Factor 3; D005346:Fibroblast Growth Factors; D006025:Glycosaminoglycans / Q000378:metabolism; D006031:Glycosylation; D006493:Heparin / Q000494:pharmacology; D051379:Mice; D010641:Phenotype; D011499:Protein Processing, Post-Translational; D011518:Proto-Oncogene Proteins / Q000378:metabolism*
D003470:Culture Media; C489197:Fgf3 protein, mouse; D051518:Fibroblast Growth Factor 3; D006025:Glycosaminoglycans; D011518:Proto-Oncogene Proteins; D005346:Fibroblast Growth Factors; D006493:Heparin