Distribution and mRNA expression of insulin-like growth factor system in pulmonary lymphangioleiomyomatosis

Background. Insulin-like growth factors (IGF-1 and IGF-2), the IGF-1 recept or (IGF-1R), and IGF-binding proteins (IGFBPs) are involved in normal pulmo nary development and in the pathogenesis of smooth muscle cell tumors. Methods: To evaluate the role of the IGF system in lymphangioleimnyomatosis (LAM), we used immunohistochemical and in situ hybridization techniques to characterize the expression of IGF-L IGF-2, IGF-IR, and IGFBP-2, -4, -5, a nd -6 in lung tissue from 18 LAM patients. Results: IGF-1, IGF-2, IGF-IR, IGFBP-1, IGFBP-2, IGFBP-4, IGFBP-5, and IGFB P-6 were expressed by LAM cells. Reactivity and mRNA expression for IGF-2 w ere observed in LAM cells and resembled that found in normal smooth muscle cells during pulmonary development as well as in smooth muscle cell tumors. IGFBP-2, IGFBP-4, and IGFBP-6 were associated with spindle-shaped LAM cell s, whereas IGFBP-5 was associated mainly with epithelioid LAM cells. Conclusions: These findings suggest that the IGFBPs modulate the effects of the IGFs on LAM cells. Thus, the patterns of localization and expression o f components of the IGF system in LAM strongly suggest that these agents ar e involved in the proliferation of LAM cells.