Keratinocyte growth factor/fibroblast growth factor 7, a homeostatic factor with therapeutic potential for epithelial protection and repair - PubMed (original) (raw)
Review
Keratinocyte growth factor/fibroblast growth factor 7, a homeostatic factor with therapeutic potential for epithelial protection and repair
Paul W Finch et al. Adv Cancer Res. 2004.
Abstract
Keratinocyte growth factor (KGF) is a paracrine-acting, epithelial mitogen produced by cells of mesenchymal origin. It is a member of the fibroblast growth factor (FGF) family, and acts exclusively through a subset of FGF receptor isoforms (FGFR2b) expressed predominantly by epithelial cells. The upregulation of KGF after epithelial injury suggested it had an important role in tissue repair. This hypothesis was reinforced by evidence that intestinal damage was worse and healing impaired in KGF null mice. Preclinical data from several animal models demonstrated that recombinant human KGF could enhance the regenerative capacity of epithelial tissues and protect them from a variety of toxic exposures. These beneficial effects are attributed to multiple mechanisms that collectively act to strengthen the integrity of the epithelial barrier, and include the stimulation of cell proliferation, migration, differentiation, survival, DNA repair, and induction of enzymes involved in the detoxification of reactive oxygen species. KGF is currently being evaluated in clinical trials to test its ability to ameliorate severe oral mucositis (OM) that results from cancer chemoradiotherapy. In a phase 3 trial involving patients who were treated with myeloablative chemoradiotherapy before autologous peripheral blood progenitor cell transplantation for hematologic malignancies, KGF significantly reduced both the incidence and duration of severe OM. Similar investigations are underway in patients being treated for solid tumors. On the basis of its success in ameliorating chemoradiotherapy-induced OM in humans and tissue damage in a variety of animal models, additional clinical applications of KGF are worthy of investigation.
Similar articles
- Effects of keratinocyte growth factor-2 (KGF-2) on wound healing in an ischaemia-impaired rabbit ear model and on scar formation.
Xia YP, Zhao Y, Marcus J, Jimenez PA, Ruben SM, Moore PA, Khan F, Mustoe TA. Xia YP, et al. J Pathol. 1999 Aug;188(4):431-8. doi: 10.1002/(SICI)1096-9896(199908)188:4<431::AID-PATH362>3.0.CO;2-B. J Pathol. 1999. PMID: 10440755 - Mouse fibroblast growth factor 10: cDNA cloning, protein characterization, and regulation of mRNA expression.
Beer HD, Florence C, Dammeier J, McGuire L, Werner S, Duan DR. Beer HD, et al. Oncogene. 1997 Oct;15(18):2211-8. doi: 10.1038/sj.onc.1201383. Oncogene. 1997. PMID: 9393979 - Neu differentiation factor/heregulin induction by hepatocyte and keratinocyte growth factors.
Castagnino P, Lorenzi MV, Yeh J, Breckenridge D, Sakata H, Munz B, Werner S, Bottaro DP. Castagnino P, et al. Oncogene. 2000 Feb 3;19(5):640-8. doi: 10.1038/sj.onc.1203357. Oncogene. 2000. PMID: 10698509 - Keratinocyte growth factor expression and activity in cancer: implications for use in patients with solid tumors.
Finch PW, Rubin JS. Finch PW, et al. J Natl Cancer Inst. 2006 Jun 21;98(12):812-24. doi: 10.1093/jnci/djj228. J Natl Cancer Inst. 2006. PMID: 16788155 Review. - Palifermin (Kepivance) for the treatment of oral mucositis in patients with hematologic malignancies requiring hematopoietic stem cell support.
Radtke ML, Kolesar JM. Radtke ML, et al. J Oncol Pharm Pract. 2005 Sep;11(3):121-5. doi: 10.1191/1078155205jp159oa. J Oncol Pharm Pract. 2005. PMID: 16390600 Review.
Cited by
- Recombinant Human Keratinocyte Growth Factor Ameliorates Cancer Treatment-Induced Oral Mucositis on a Chip.
Ly KL, Rajtboriraks M, Elgerbi A, Luo X, Raub CB. Ly KL, et al. Adv Healthc Mater. 2024 Jun;13(14):e2302970. doi: 10.1002/adhm.202302970. Epub 2024 Feb 22. Adv Healthc Mater. 2024. PMID: 38351394 - Primary and secondary defects of the thymus.
Dinges SS, Amini K, Notarangelo LD, Delmonte OM. Dinges SS, et al. Immunol Rev. 2024 Mar;322(1):178-211. doi: 10.1111/imr.13306. Epub 2024 Jan 16. Immunol Rev. 2024. PMID: 38228406 Review. - Fish Collagen Peptides Enhance Thymopoietic Gene Expression, Cell Proliferation, Thymocyte Adherence, and Cytoprotection in Thymic Epithelial Cells via Activation of the Nuclear Factor-κB Pathway, Leading to Thymus Regeneration after Cyclophosphamide-Induced Injury.
Lee DY, Song WH, Lim YS, Lee C, Rajbongshi L, Hwang SY, Kim BS, Lee D, Song YJ, Kim HG, Yoon S. Lee DY, et al. Mar Drugs. 2023 Oct 12;21(10):531. doi: 10.3390/md21100531. Mar Drugs. 2023. PMID: 37888466 Free PMC article. - Functional Distinctions of Endometrial Cancer-Associated Mutations in the Fibroblast Growth Factor Receptor 2 Gene.
Dixit G, Pappas BA, Bhardwaj G, Schanz W, Maretzky T. Dixit G, et al. Cells. 2023 Sep 7;12(18):2227. doi: 10.3390/cells12182227. Cells. 2023. PMID: 37759450 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical