THE INSULIN-LIKE GROWTH-FACTOR BINDING-PROTEINS (IGFBPS) IN HUMAN BREAST-CANCER

Several lines of evidence suggest that IGFs are important regulators of breast cancer cell growth. Unlike other growth factors, the IGFs interact with specific binding proteins in all extracellular fluids. To date, six different IGFBPs have been cloned, although their exact physiological function is not understood. Experimental evidence accumulated over the past few years suggests that IGFBPs could function as modulators of IGF actions in a variety of systems. This includes breast cancer, since several groups have demonstrated the production of IGFBPs by human breast cancer cells. We have found that the pattern of expression of these binding proteins is heterogeneous and varies depending on the breast cancer cell ER status. We have also shown that estrogen is capable of regulating the expression of certain IGFBPs in MCF-7 cells. Specifically, estradiol enhanced the expression of IGFBP 2, 4, and 5, and decreased that of IGFBP-3 in this cell line. Since the IGFBPs can modulate IGF actions in different experimental systems, we and others have studied their potential role as inhibitors of IGF-induced mitogenesis in breast cancer cells. We have demonstrated that purified IGFBP-1 neutralized IGF-dependent growth of MCF-7 cells in a reversible manner. These results suggest that the IGFBPs might be used to inhibit IGF-mediated breast cancer proliferation.