[Impact on tumor angiogenesis and tumor progression of expression of the 18 kd and 24 kd isoforms of FGF-2].
The role of FGF-2 in tumor progression and tumor cell invasiveness was investigated using the rat bladder carcinoma cells NBT-II, which do not constitutively express FGF-2 or its membrane-spanning receptor. The NBT-II cells were transfected using expression vectors encoding either the 18 kD or the 24 kD isoform of FGF-2. The 24 kD isoform contains a nuclear localization signal. The transfected NBT-II cells that expressed 18 kD FGF-2 produced and secreted this factor as the biologically active form and retained an epithelial morphology. When injected to nude mice, the tumorigenic potential of these cells was not increased over that of non-transfected NBT-II cells; however, although the time to tumor development was long, the tumors were highly vascularized, indicating secretion of the angiogenic factor FGF-2. The transfected NBT-II cells that expressed 24 kD FGF-2 varied in their morphological appearance and did not secrete FGF-2; immunofluorescence and Western-blot studies showed that the FGF-2 was mainly intranuclear. When injected to nude mice, these cells produced tumors and migrated not only to the lymph nodes but also to the lungs where they produced metastases. In aggregate, these data indicate that stimulation of angiogenesis is not sufficient to increase tumor growth and that nuclear FGF-2 acts as a tumorigenic and metastasis-promoting factor in the NBT-II carcinoma model.
Okada-Ban
M
M
UMR 144 CNRS, Institut Curie, Paris, France.
Grassi
M
M
Plouet
J
J
Thiery
J P
JP
Jouanneau
J
J
D000818:Animals; D018450:Disease Progression; D016222:Fibroblast Growth Factor 2 / Q000502:physiology*; D006801:Humans; D051379:Mice; D008970:Molecular Weight; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic; D051381:Rats; D014407:Tumor Cells, Cultured
D016222:Fibroblast Growth Factor 2
Impact sur l'angiogenèse tumorale et la progression tumorale de l'expression des isoformes 18 kD et 24 kD du FGF-2.