THE INSULIN-LIKE GROWTH-FACTOR-1 RECEPTOR IS EXPRESSED BY EPITHELIAL-CELLS WITH PROLIFERATIVE POTENTIAL IN HUMAN EPIDERMIS AND SKIN APPENDAGES - CORRELATION OF INCREASED EXPRESSION WITH EPIDERMAL HYPERPLASIA

Ligand-mediated activation of the insulin-like growth factor 1 (IGF-1) receptor is critical for epidermal keratinocyte proliferation in vitr o, and its expression in normal and psoriatic epidermis suggests that it might regulate keratinocyte proliferation in vivo, In this study, w e used a monoclonal antibody (alpha-IR(3)) that binds to the alpha-cha in of this receptor to study its expression (i) in other epithelial ce ll types in human skin and (ii) in growth-activated epidermis associat ed with various cutaneous pathologies. In normal skin, IGF-1 receptors were expressed by basal epidermal keratinocytes as well as by basal-l ike or undifferentiated germinative epithelial cells associated with t he follicular outer root sheath, sebaceous glands, and the hair matrix , There was minimal IGF-1 receptor expression in differentiating outer root sheath, hair shaft, and sebaceous epithelial cells, IGF-1 recept or expression in non-growth-activated epidermis of long-standing sebor rheic keratoses was confined to the basal epidermal layer, as in norma l epidermis, In contrast, hyperplastic epidermis undergoing ''regenera tive'' differentiation (keratin 16(+), Ki67(+) suprabasal keratinocyte s) from psoriasis, chronic skin wounds, and plaques of mycosis fungoid es consistently showed increased expression of IGF-1 receptor, In thes e conditions, the region of expanded IGF-1 receptor expression delimit ed the epidermal zone of keratinocyte proliferation, In cultured kerat inocytes, the subcellular localization of the IGF-1. receptor could be modulated from plasma membranes to the cell cytoplasm by ligand bindi ng, suggesting that the in vivo cytoplasmic staining occasionally obse rved represents internalization of receptors following ligand stimulat ion, Our results suggest that cell surface IGF-1 receptors are widely expressed by epithelial cells with proliferative potential, that recep tor expression can be modulated with differing epidermal growth states , and that these receptors are largely downregulated in highly differe ntiated epithelial cells.