IGF and prostate cancer

 Insulin-like growth factors (IGFs) are protein hormones that circulate in the blood and appear to be important in cellular growth, division and differentiation. IGFs share functional and structural similarities with insulin. Of the two IGFs (IGF-I and IGF-II), IGF-I seems to have the strongest affinity to the important receptor (IGF-IR) located on the cell surface, meaning that it “binds” to the receptor. This causes a cascade of reactions that eventually turn on the “cell growth machinery.” Interestingly, these hormones affect cell growth and differentiation in ways similar to the manner in which cancer cells divide and grow. Research in the last decade has revealed growing evidence to suggest that IGF-I is involved in various malignancies. Studies in men with prostate cancer have shown that circulating IGF-I levels are positively associated with the increased risk of prostate cancer. These levels are found to be elevated many years prior to the detection of the cancer, suggesting a causal role. These studies have been confirmed by recent research in human prostate cancer tissue. Further, laboratory experiments have shown that IGF-I causes prostate cancer cells to proliferate and also interferes with the effects of various treatments. Research has also revealed that both IGF-I and IGF-II are modulated by a set of binding proteins (IGFBPs) that effectively block their interaction with the receptor. The most abundant IGFBP, IGFBP-3, has growth-inhibitory properties, while IGFBP-2 and -5 seem to promote cellular growth and proliferation. IGFBPs are thought to be crucial in the function of IGF-I. Although levels of IGF-I or IGFBPs in the blood are not currently used to screen for prostate cancer, research labs in Canada and around the world are trying to clarify their role in this disease. Novel prostate cancer therapies that target IGF-I, IGF-IR or IGFBPs are now in development.