Overexpression of insulin-like growth factor-1 (IGF-I) receptor and the invasiveness of cultured keloid fibroblasts

Keloid is a dermal fibroproliferative tissue of unknown etiology. Protein t yrosine kinases (PTKs) play an important role in the regulation of cell gro wth and differentiation. Activation of PTK cascades In keloid fibroblasts i s thought to be closely linked to abnormal cell proliferation and migration , We determined the expression profile of PTK genes in normal skin and kelo id fibroblasts using the homology cloning method with a degenerated primer. Eight PCK genes were expressed among a total of 46 receptor-type clones. T he most abundant type of PTK receptors was the platelet-derived growth fact or receptor in both fibroblasts. However, insulin-like growth factor-I rece ptor (IGF-IR) was overexpressed only in keloid-derived fibroblasts (9 of 24 ), Immunohistochemical analysis confirmed the high expression of IGF-IR in keloid fibroblasts, but not in normal fibroblasts. To examine the functiona l properties of the IGF-I/GF-IR pathway, we investigated cell proliferation and invasion activities of both types of fibroblasts, The mitogenic effect of IGF-I on both fibroblasts was very weak compared with serum stimulation . In contrast, the invasive activity of keloid fibroblasts was markedly inc reased in the presence of IGF-I, and inhibited by a neutralizing antibody a gainst IGF-IR. tur results indicate the involvement of activated IGF-I/IGF- IR in the pathogenesis of keloid by enhancing the invasive activity of fibr oblasts.