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.