Regulation of insulin-like growth factors and IGF-binding proteins in bone tumours

Insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) are important regulators of growth and development in normal bone and bone tumours. IGFs contribute to about 50% of basal bone cell proliferation. Their mitogenic action is either enhanced or inhibited by specific IGFBPs which are also regulated by a variety of factors. This system is further complicated by the presence of specific proteases for IGFBPs. Serine proteases are secreted by malignant bone tumours and the hydrolysis of IGFBPs increases the bioavailability of IGFs. In addition, the autocrine production of IGFs may facilitate the development of bone tumours and metastatic lesions.