Tissue distribution and retinoid-mediated downregulation of an FGF-bindingprotein (FGF-BP) in the rat

We showed previously that a secreted fibroblast growth factor-binding prote in (FGF-BP) can mobilize and bioactivate locally-stored FGFs from the extra cellular matrix. This FGF-BP is upregulated in carious cancers and plays a rate limiting role as an angiogenic switch molecule during tumor growth, In this paper, ne describe the cloning and sequence analysis of the rat homol ogue of FGF-BP and show its expression pattern and retinoid-mediated downre gulation in normal adult rat tissues. The rat FGF-BP amino acid sequence is 91% and 70% homologous to mouse and human, respectively, and contains 10 c ysteine residues whose position is conserved across species, In Northern bl ots, FGF-BP mRNA was detected in the gut, eye, thymus, skin, lung and tongu e. Immunohistochemistry confirmed this tissue distribution with cerebellar Purkinje cells, the cerebral chorioid plexus and the eye showing the most d istinctive staining patterns. Oral treatment of animals with all-rr arts-re tinoic acid for one and two days induced a significant decrease of FGF-BP p rotein in tissues from stomach, eye and lung suggesting that regulation of FGF-BP can be one effector mechanism through which retinoids affect normal and pathological processes.