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Epidermal growth factor (EGF)‐ and scatter factor/hepatocyte growth factor (SF/HGF)‐mediated keratinocyte migration is coincident with induction of matrix metalloproteinase (MMP)‐9
Author(s) -
McCawley Lisa J.,
O'Brien Patricia,
Hudson Laurie G.
Publication year - 1998
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/(sici)1097-4652(199808)176:2<255::aid-jcp4>3.0.co;2-n
Subject(s) - hepatocyte growth factor , microbiology and biotechnology , epidermal growth factor , receptor tyrosine kinase , biology , growth factor , hepatocyte growth factor receptor , epidermal growth factor receptor , growth factor receptor , platelet derived growth factor receptor , growth factor receptor inhibitor , tyrosine kinase , signal transduction , cancer research , receptor , c met , biochemistry
Receptor tyrosine kinases are key regulators of cellular function including cell growth, differentiation, migration, and morphogenesis. Disruptions of receptor tyrosine kinase signaling pathways are often associated with changes in cellular proliferative capacity and tumorigenesis. Both receptor‐specific and cell type‐specific factors may contribute to the ultimate cellular responses observed after receptor activation. In this regard, we find that both normal keratinocytes and their tumorigenic counterparts display differential responses to activation of receptor tyrosine kinases. Multiple ligands were mitogenic for keratinocytes, but only epidermal growth factor (EGF), transforming growth factor α (TGFα), and scatter factor/hepatocyte growth factor (SF/HGF) promoted cell motility as assessed by colony dispersion (scattering) and in vitro reepithelialization. Interestingly, growth factor specificity for motility coincided with ligand‐mediated cell invasion through a reconstituted basement membrane and induction of the 92‐kDa metalloproteinase (MMP‐9) activity as determined by gelatin zymogram analysis. Inhibitors of MMP activity or addition of an MMP‐9 neutralizing antibody resulted in the loss of growth factor‐induced colony dispersion, suggesting a functional role for MMP‐9 induction during this response. Coordinate regulation of MMP‐9 induction and the migratory response are likely to contribute to the enhanced invasive potential observed in response to EGF and SF/HGF. Our findings suggest that alternate receptor‐mediated signaling pathways leading to differences in gene expression may be involved in complex cellular responses such as colony dispersion or invasion. J. Cell. Physiol. 176:255–265, 1998. © 1998 Wiley‐Liss, Inc.