The Role of the Insulin-like Growth Factor System in Human Cancer

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This chapter focuses on the role of the insulin-like growth factor system in human cancer. The normal process of growth and differentiation results from the genetically programmed action of a number of different cellular and extracellular factors. Derangement in the function of one or more of those agents can result in a pathologic phenotype, including neoplastic growth. A family of growth factors shown to be intimately involved in the regulation of cell growth as well as in cellular transformation is the insulin-like growth factor (IGF) family. IGF-I and IGF-II are mitogenic polypeptides produced in the largest amounts by the liver and secreted into the circulation, where they mediate the effects of growth hormone (GH) on longitudinal growth. In addition to ligands and receptors, the IGF system comprises a third category of molecules, which bind IGFs in the circulation and in extracellular compartments. Six IGF-binding proteins (IGFBPs) have been characterized to date. Binding of IGFs to the IGF-I receptor induces receptor autophosphorylation. The cell cycle consists of four major phases: (1) the presynthetic phase, G; (2) the phase of DNA synthesis, S; (3) the premitotic phase, G; and (4) mitosis, M. IGF-I, IGF-II, and insulin are chemotactic agents for the human melanoma cell line A2058, as assayed in a modified Boyden chamber. The chapter also gives selected examples of IGF involvement in human cancer. The wealth of information generated in the IGF field, as well as continued research efforts, both basic and clinic, promise to produce rational therapeutic approaches for those cancers in which the IGF system is involved.

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