GROWTH FACTOR-INDUCED EPIDERMAL INVASION OF THE DERMIS IN HUMAN SKIN ORGAN-CULTURE - DERMAL INVASION CORRELATED WITH EPITHELIAL-CELL MOTILITY

We have developed a model of human squamous epithelial cell invasion i n human skin organ culture, Epidermal invasion of the dermis occurs in this model when the tissue is exposed to an exogenous source of epith elial cell growth factor. In the present study we sought to determine to what extent growth factor-induced invasion correlates with the abil ity of the growth factor to induce epithelial cell motility, Histologi cal examination of tissue treated with epidermal growth factor (EGF), hepatocyte growth factor (HGF), insulin-like growth factor-1 (IGF-1) o r keratinocyte growth factor (KGF) showed that only HGF and EGF were i nducers of invasion while KGF- and IGF-1-treated tissues were histolog ically similar to untreated controls. In parallel studies, HGF and EGF were found to be potent stimulators of epidermal keratinocyte motilit y while IGF-1 was less effective and KGF was even less so. None of the growth factors stimulated dermal fibroblast motility while HGF and to a lesser extent IGF-1 (but not EGF or KGF) stimulated motility of der mal vascular endothelial cells. Thus, there is a strong correlation be tween growth factor capacity to induce epidermal keratinocytes to inva de the underlying dermal tissue and to induce motility in the invasive population of cells.