Autocrine transformation by fibroblast growth factor 9 (FGF-9) and its possible participation in human oncogenesis

Int J Cancer. 1997 May 2;71(3):442-50. doi: 10.1002/(sici)1097-0215(19970502)71:3<442::aid-ijc23>;2-g.


Transfection of human fibroblast growth factor 9 (FGF-9) cDNA into mouse BALB/c 3T3 clone A31 cells led to morphological transformation of the cells and foci formation 4 weeks later. Isolated transformants had a higher saturation density than parental A31 cells, could grow in soft agar, and secreted FGF-9 into the culture supernatant. The introduction of FGF-9 N33 cDNA, which encodes a truncated protein that has 33 N-terminal amino acids deleted and has the same mitogenic potency as FGF-9, failed to lead to foci formation. Although FGF-9 is a secretory protein, it does not have a typical secretory signal sequence, and the secreted protein retains the full sequence coded in the cDNA except for the initiating methionine. The produced FGF-9 N33 was not secreted and remained within the cell. It is possible that FGF-9 has an uncleavable signal sequence within the first 33 N-terminal amino acids. All of the phenotypes acquired by transformation could be arrested by treatment with a neutralizing anti-human FGF-9 monoclonal antibody (MAb) 150-59. Additionally, transformants formed tumors in nude mice. Injection of MAb 150-59 suppressed tumor formation in nude mice and caused existing tumors to regress. Our results suggest that the cellular transformation mediated by FG F-9 is produced by autocrine stimulation. We have detected FGF-9 production in the human tumor cell lines glioma NMC-G1, from which FGF-9 was originally purified, and stomach carcinoma AZ-521. The growth of NMC-G1 was not affected by MAb 150-59, but that of AZ-521 was arrested by MAb 150-59 in the presence of heparin. Moreover, the growth of the AZ-521 cell tumor in nude mice could be partially arrested by antibody treatment. The possibility of a participation of FGF-9 in the formation of human tumors is suggested.

MeSH terms

  • 3T3 Cells
  • Animals
  • Antibodies, Monoclonal / pharmacology
  • COS Cells
  • Cell Division
  • Cell Line
  • Cell Transformation, Neoplastic*
  • Clone Cells
  • DNA, Complementary
  • Fibroblast Growth Factor 9
  • Fibroblast Growth Factors*
  • Glioma / pathology*
  • Growth Substances / biosynthesis
  • Growth Substances / immunology
  • Growth Substances / physiology*
  • Humans
  • Mice
  • Mice, Nude
  • Oncogenes*
  • Recombinant Proteins / biosynthesis
  • Stomach Neoplasms / pathology*
  • Transfection
  • Transplantation, Heterologous
  • Tumor Cells, Cultured


  • Antibodies, Monoclonal
  • DNA, Complementary
  • FGF9 protein, human
  • Fgf9 protein, mouse
  • Fibroblast Growth Factor 9
  • Growth Substances
  • Recombinant Proteins
  • Fibroblast Growth Factors