Ligand-mediated activation of the insulin-like growth factor 1 (IGF-1) receptor is critical for epidermal keratinocyte proliferation in vitro, and its expression in normal and psoriatic epidermis suggests that it might regulate keratinocyte proliferation in vivo. In this study, we used a monoclonal antibody (alpha-IR3) that binds to the alpha-chain of this receptor to study its expression (i) in other epithelial cell types in human skin and (ii) in growth-activated epidermis associated with various cutaneous pathologies. In normal skin, IGF-1 receptors were expressed by basal epidermal keratinocytes as well as by basal-like or undifferentiated germinative epithelial cells associated with the 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 receptor expression in non-growth-activated epidermis of long-standing seborrheic keratoses was confined to the basal epidermal layer, as in normal epidermis. In contrast, hyperplastic epidermis undergoing "regenerative" differentiation (keratin 16+, Ki67+ suprabasal keratinocytes) from psoriasis, chronic skin wounds, and plaques of mycosis fungoides consistently showed increased expression of IGF-1 receptor. In these conditions, the region of expanded IGF-1 receptor expression delimited the epidermal zone of keratinocyte proliferation. In cultured keratinocytes, the subcellular localization of the IGF-1 receptor could be modulated from plasma membranes to the cell cytoplasm by ligand binding, suggesting that the in vivo cytoplasmic staining occasionally observed represents internalization of receptors following ligand stimulation. Our results suggest that cell surface IGF-1 receptors are widely expressed by epithelial cells with proliferative potential, that receptor expression can be modulated with differing epidermal growth states, and that these receptors are largely downregulated in highly differentiated epithelial cells.

No abstract

Growth of normal melanocytes, nevus cells and primary melanoma cells is enhanced by insulin/insulin-like growth factor-I (IGF-I) in vitro. It has been shown that a melanoma cell line possesses the IGF-I receptor which plays a role in activation of the chemotactic response. Little is known about the in vivo expression of the IGF-I receptor and its role in melanocytic lesions. In an immunohistochemical study, we investigated the expression of IGF-I receptor in frozen sections of congenital pigmented nevi from 10 patients (ages 8 months to 4 yrs) using the monoclonal antibody alpha IR3, which specifically recognizes the extracellular alpha subunit of the IGF-I receptor. The proliferative activity of the nevus cells was examined by staining with Ki67 monoclonal antibody (reactive with all actively cycling cells). IGF-I receptor was found to be widely expressed by the cell surface of the nevus cells. Membrane staining was occasionally stronger in the superficial portion of the congenital pigmented nevi. In contrast, Ki67-positive cells were only sparsely scattered throughout the nevi with some tendency to localization to the superficial portion. This study indicates that in vivo the IGF-I receptor is widely expressed by congenital pigmented nevus cells. As opposed to keratinocytes, in which IGF-I receptor expression defines the proliferation pool of the normal and disordered epidermis, the IGF-I receptor is expressed by all nevus cells, irrespective of their proliferative status. Further studies are needed to assess whether the IGF-I receptor expression can serve as a marker for increased risk for development of malignancy in various types of benign melanocytic lesions.

No abstract

No abstract