Characterization of Recombinant Human Fibroblast Growth Factor (FGF)-10 Reveals Functional Similarities with Keratinocyte Growth Factor (FGF-7)

Abstract

A newly identified member of the fibroblast growth factor (FGF) family, designated FGF-10, is expressed during development and preferentially in adult lung. The predicted FGF-10 protein is most related to keratinocyte growth factor (KGF, or FGF-7). The latter is unique among FGFs in that it binds and signals only through the FGF receptor (FGFR2b) isoform KGF receptor (KGFR) expressed specifically by epithelial cells. In order to examine the biological and biochemical properties of human FGF-10, we isolated the cDNA and expressed its encoded protein in bacteria. The recombinant protein (rFGF-10) was a potent mitogen for Balb/MK mouse epidermal keratinocytes with activity detectable at 0.1 nM and maximal at around 5 nM. Within this concentration range, FGF-10 did not stimulate DNA synthesis in NIH/3T3 mouse fibroblasts. rFGF-10 bound the KGFR with high affinity comparable to that of KGF, and did not bind detectably to either the FGFR1c (Flg) or FGFR2c (Bek) receptor isoforms. The mitogenic activity of FGF-10 could be distinguished from that of KGF by its different sensitivity to heparin and lack of neutralization by a KGF monoclonal antibody. These results indicate that FGF-10 and KGF have similar receptor binding properties and target cell specificities, but are differentially regulated by components of the extracellular matrix.

Maintenance of surfactant protein A and D secretion by rat alveolar type II cells in vitro

“…However, the difference between KGF and FGF-10 was surprising. Both are thought to recognize the same receptor (20,29). Presumably, there are costimulatory molecules or other subtle differences in the receptor signaling that are presently not known that account for this difference.…”

“…1, KGF was the only growth factor that stimulated the production and secretion of significant amounts of SP-A or SP-D. This was surprising, because FGF-10 is very similar to KGF, binds the same FGF receptor splice variant (FGFR-2IIIb) (20,29), and stimulates type II cell proliferation in vivo. The morphology of type II cell cultures without KGF was that of a flat monolayer, whereas the cultures with KGF had areas of refractile cuboidal cells.…”

Growth factor – regulated expression of enzymes involved in nucleotide biosynthesis: a novel mechanism of growth factor action

“…Thereby the recently identi®ed ®broblast growth factor 10 (FGF-10) is the most likely candidate, since it binds to the KGF receptor (a splice variant of FGFreceptor 2) with high a nity (Igarashi et al, 1998). Furthermore, both KGF and FGF-10 have a similar expression pattern in adult mouse tissues (Beer et al, 1997).…”

Fgf10 is an oncogene activated by MMTV insertional mutagenesis in mouse mammary tumors and overexpressed in a subset of human breast carcinomas

“…The presence of the FGF10 protein in the HC11-Fgf10-transduced cells was confirmed by Western blot analysis (Figure 2b). We verified Wnt1 protein production in HC11-Wnt1 using the pTOP-FLASH/ pFOPFLASH assay (van de Wetering et al, Fgf10-expressing HC11 cells exhibit increased proliferation in vitro FGF10 is mitogenic for epithelial cells (Igarashi et al, 1998), most likely through the activation of the MAPK pathway (Taniguchi et al, 2003). We tested the mitogenic effect of Fgf10 expression in HC11 cells in an in vitro proliferation assay.…”