Responses of keratinocytes to substrate-bound vitronectin: growth factor complexes.
Insulin-like growth factor-1 (IGF-I) can associate with the extracellular matrix protein vitronectin (VN) via select IGF-binding proteins, and the resulting complex stimulates responses in a variety of cell types. As VN can also associate with epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF), we hypothesized that the multimeric nature of VN could be exploited to deliver multiple growth factors to the cell surface. We report here that VN enhances bFGF but not EGF stimulated [(3)H]-leucine incorporation in the HaCAT keratinocyte cell line, with VN synergistically enhancing cell migration in response to both EGF and bFGF when presented as a VN-bound complex. Furthermore, the addition of EGF and/or bFGF to IGF-I:IGFBP-5:VN complexes significantly enhances both [(3)H]-leucine incorporation and migration of HaCAT cells above that induced by IGF:IGFBP-5:VN complexes alone. Indeed, similar responses are observed in primary cultures of human skin keratinocytes, highlighting the potential use of these novel complexes for a wide range of tissue repair applications.
Hollier
Brett
B
Tissue BioRegeneration and Integration Program, Science Research Centre, School of Life Sciences, Queensland University of Technology, GPO Box 2434, Brisbane, Queensland 4001, Australia. b.hollier@qut.edu.au
Harkin
Damien G
DG
Leavesley
David
D
Upton
Zee
Z
D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D008855:Microscopy, Electron, Scanning; D012867:Skin / Q000166:cytology; D019096:Vitronectin / Q000494:pharmacology*
D006133:Growth Substances; D019096:Vitronectin; D016222:Fibroblast Growth Factor 2; D004815:Epidermal Growth Factor