Keratinocyte growth factor as a cytokine that mediates mesenchymal-epithelial interaction.
Keratinocyte growth factor (KGF) is a member of the heparin-binding fibroblast growth factor family (FGF-7) with a distinctive pattern of target-cell specificity. Studies performed in cell culture suggested that KGF was mitogenically active only on epithelial cells, though from a variety of tissues. In contrast, KGF was produced solely by cells of mesenchymal origin, leading to the hypothesis that it might function as a paracrine mediator of mesenchymal-epithelial communication. Biochemical analysis and molecular cloning established that the KGF receptor (KGFR) was a tyrosine kinase isoform encoded by the fgfr-2 gene. Many detailed investigations of KGF and KGFR expression in whole tissue and cell lines largely substantiated the pattern initially perceived in vitro of mesenchymal and epithelial distribution, respectively. Moreover, functional assays in organ culture and in vivo and analysis of agents regulating KGF expression reinforced the idea that KGF acts predominantly on epithelial cells. While the data do not implicate a KGF autocrine loop in neoplasia, paracrine sources of factor or ligand-independent signaling by the KGFR might contribute to malignancy. Alternatively, because of its differentiation-promoting effects, KGF may retard processes that culminate in uncontrolled cell growth.
Rubin
J S
JS
Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, MD 20892, USA.
Bottaro
D P
DP
Chedid
M
M
Miki
T
T
Ron
D
D
Cunha
G R
GR
Finch
P W
PW
D000818:Animals; D002450:Cell Communication; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D016207:Cytokines / Q000502:physiology*; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D051526:Fibroblast Growth Factor 10; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D015870:Gene Expression; D006133:Growth Substances / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D008648:Mesoderm / Q000502:physiology*; D051379:Mice; D008954:Models, Biological; D009369:Neoplasms / Q000473:pathology / Q000503:physiopathology; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D051497:Receptor, Fibroblast Growth Factor, Type 2; D017468:Receptors, Fibroblast Growth Factor; D017978:Receptors, Growth Factor / Q000096:biosynthesis / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014945:Wound Healing / Q000187:drug effects
D016207:Cytokines; C496453:FGF7 protein, human; C496454:Fgf7 protein, mouse; D051526:Fibroblast Growth Factor 10; D006133:Growth Substances; D017468:Receptors, Fibroblast Growth Factor; D017978:Receptors, Growth Factor; D011994:Recombinant Proteins; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D020794:Receptor Protein-Tyrosine Kinases; D051497:Receptor, Fibroblast Growth Factor, Type 2; C065104:keratinocyte growth factor receptor