Nuclear FGF-2 facilitates cell survival in vitro and during establishment of metastases.
Nuclear-targeted high molecular weight 24 kDa fibroblast growth factor 2 (FGF-2) may induce specific cell functions through intracrine mechanisms. The role of nuclear FGF-2 on the metastatic potential of carcinoma cells was examined by conditional FGF-2 expression, which demonstrated that spontaneous metastasis in nude mice is a direct consequence of its expression. The lung colonizing capacities of fluorescent nuclear FGF-2-expressing cells following intravenous injection was also investigated. All cells reaching the lung extravasated as soon as 5 min following injection with similar in vivo behavior during the first 24 h. However, after 2 days, dramatic differences were observed between the FGF-2 and parental cells: most control cells underwent apoptosis, while the FGF-2-producing cells instigated a survival program and proliferated. Therefore, sustained apoptosis in vivo prevents growth of metastatic foci, while nuclear FGF-2 induction of a survival program is responsible for growth of the lung metastases. In vitro serum deprivation assays also established that 24 kDa FGF-2 expression improves carcinoma cell survival. This study provides both in vitro and in vivo evidence that the role of the nuclear 24 kDa FGF-2 isoform in carcinoma is the promotion of cell survival, thereby defining its association with poor prognosis in some human carcinomas.
Thomas-Mudge
Rachel J
RJ
UMR144 CNRS, Institut Curie, Research Division, 26 rue d'Ulm, 75248 Paris 05, France.
Okada-Ban
Maï
M
Vandenbroucke
Franck
F
Vincent-Salomon
Anne
A
Girault
Jeanne-Marie
JM
Thiery
Jean-Paul
JP
Jouanneau
Jacqueline
J
D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000737:chemistry; D002470:Cell Survival / Q000235:genetics*; D002999:Clone Cells; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism*; D007279:Injections, Subcutaneous; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary*; D051379:Mice; D008819:Mice, Nude; D008970:Molecular Weight; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D051381:Rats; D014183:Transplantation, Heterologous; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology
D020033:Protein Isoforms; D016222:Fibroblast Growth Factor 2