Role of epidermal growth factor receptor in basal and stimulated colonic epithelial cell migration in vitro

Colonic mucosal wounds are repaired, in part, by epithelial migration. Sign aling mechanisms regulating this migration are poorly characterized. This s tudy aimed to examine the role that the epidermal growth factor (EGF) recep tor (EGF-R) and its ligands, EGF and transforming growth factor-alpha (TGF- alpha), play in migration in wounded in vitro models of colonic epithelium. Migration was assessed over 24 h in circular wounds made in confluent mono layers of LIM1215 human colon cancer cells. EGF and TGF-alpha stimulated mi gration twofold from 4 h after wounding. Basal migration and the motogenic effects of short chain fatty acids and hepatocyte growth factor were mediat ed through enhanced binding of TGF-alpha to EGF-R, while trefoil peptide-me diated motogenesis required EGF-R activation independently of TGF-alpha bin ding. Activation of protein kinase C (PKC) stimulated migration, an effect more potent than, and independent of, EGF-R activation. However, neither in hibition of PKC by Ro 31-8220 nor depletion of PKC by pretreatement with ph orbol myristate acetate attenuated EGF-R-mediated motogenesis. In conclusio n, EGF-R activation via TGF-alpha binding, or intracellularly, mediates bas al LIM1215 migration and the effects of several motogens, with the exceptio n of PKC activators. Since EGF-R and PKC have physiological activators in v ivo, they may control colonic mucosal repair processes following injury. (C ) 1999 Academic Press.