Expression of a binding protein for FGF is associated with epithelial development and skin carcinogenesis

Abstract

Fibroblast growth factors (FGF)-1 and -2 are found in most embryonic and adult normal and tumor tissues, where they are immobilized in the extracellular matrix (EM). Mobilization of these FGFs is part of a tightly controlled process resulting in the activation of high-affinity receptors. Recently, we have shown that a novel human FGF-binding protein (FGF-BP) mediates the release of immobilized FGF-2 from the EM. Here we isolated genomic and cDNA clones of the mouse FGF-BP homologue and studied its expression during embryonic development and skin carcinogenesis. The murine gene contains two exons that generate a 1.2 kb mRNA and predicts an 18 kDa secreted protein that is 63% identical to its human homologue. FGF-BP mRNA expression during embryogenesis is restricted to skin, intestine and lung. In the developing skin, FGF-BP expression starts at embryonic day 9, reaches peak levels perinatally and is downregulated during postnatal development. Develepment regulation in the intestine is similar, but in lungs and ovaries high expression was also observed in the adult. FGF-BP mRNA expression in the adult skin is dramatically increased during early stages of carcinogen-induced transformation in vivo and by ras-activation in vitro. Finally, mouse FGF-BP binds to FGF-2 and can function as a modulator of FGF in FGF-responsive cells. Our results suggest a potential function of FGF-BP during development and tumorigenesis.