Insulinlike growth factors and binding proteins in colon cancer.

Insulinlike growth factors (IGFs) express anabolic and mitogenic activity on wide variety of cells. Besides endocrine effects, IGFs have major autocrine and paracrine effects on many cellular functions. Two factors that significantly affect the extent of cellular response to IGFs include the membrane receptors for IGFs and the soluble binding proteins (BPs), which modulate the action of IGFs at the receptor level. IGFs, IGF receptors, and IGFs and their BPs (IGF-BPs) thus constitute three components of the IGF system. A role of IGFs in the transformation and proliferation of cancer cells has become increasingly evident in the past few years. Studies from several laboratories show that all three components of the IGF system may play an important role in the proliferation of colon cancers. It was recently shown that the relative expression of IGFs and IGF/BPs may critically control the metastatic potential of colon cancers. The purpose of this article is to summarize our current knowledge of the IGF system and to present support for a significant role of IGFs in the initiation and growth of colon cancers. The expression and structural aspects of IGFs, their receptors, and BPs are outlined first, followed by a discussion of the role of IGFs in gastrointestinal functions and in colon cancers.