Nuclear 24 kD fibroblast growth factor (FGF)-2 confers metastatic properties on rat bladder carcinoma cells.
The tumorigenic and metastatic properties of rat bladder carcinoma NBT-II cells transfected with a cDNA encoding the 24 kD nuclear isoform of human fibroblast growth factor-2 (FGF-2) were analysed and compared with those cells producing the 18 kD cytoplasmic isoform FGF-2. In transfected clones, 24 kD FGF-2 was found in the nucleus, and no FGF-2 was secreted. RT-PCR analysis showed no upregulation of FGF-2-specific receptor FGFR2c expression in these proliferating transfected cells. A shorter latency period for in vivo tumor formation and abundant spontaneous lung metastases were only seen if nuclear FGF-2-producing cells were injected subcutaneously into nude mice. Intravenous injection of 24 kD FGF-2-producing cells led to extensive experimental lung metastases whereas injection of control NBT-II cells or 18 kD FGF-2-producing cells did not. As FGF-2-producing cells have no specific FGF-2 receptors, our results suggest that the 24 kD FGF-2 has nuclear targets, and activates metastatic property of carcinoma cells via a mechanism other than the conventional FGF receptor-mediated signaling pathway.
Okada-Ban
M
M
UMR144 CNRS, Institut Curie, Section de recherche, Paris, France.
Moens
G
G
Thiery
J P
JP
Jouanneau
J
J
D000818:Animals; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis / Q000502:physiology*; D006801:Humans; D008175:Lung Neoplasms / Q000556:secondary*; D051379:Mice; D008819:Mice, Nude; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D051497:Receptor, Fibroblast Growth Factor, Type 2; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*
D017468:Receptors, Fibroblast Growth Factor; D016222:Fibroblast Growth Factor 2; C496353:FGFR2 protein, human; C496354:Fgfr2 protein, mouse; C496356:Fgfr2 protein, rat; D020794:Receptor Protein-Tyrosine Kinases; D051497:Receptor, Fibroblast Growth Factor, Type 2