IGFBPs and neoplastic models. New concepts for roles of IGFBPs in regulation of cancer cell growth.

The insulin-like growth factor binding proteins (IGFBPs) are a family of seven structurally homologous proteins that bind insulin-like growth factor 1 (IGF-I) and IGF-II with high affinity, thereby modu-lating the actions of IGFs. Several lines of recent evidence from various cell systems have suggested that IGFBPs, especially IGFBP-3, may play more active, IGF-independent, roles in growth regulation of cancer cells. In support of this hypothesis, the author has recently shown that IGFBP-3 binds specifically and with high affinity to the surface of various cell types and directly inhibits monolayer growth of these cells in an IGF-independent manner, presumably by specific interaction with cell membrane proteins that function as an IGFBP-3 receptor. The author's current studies demonstrate that a new class of IGFBP, IGFBP-7, constitutes a low affinity member of the IGFBP family, but primarily functions as a modulator of cell growth in an IGF-independent manner, similar to the action observed with IGFBP-3 in breast cancer cells. The author's studies on the mechanisms of action of the low affinity IGFBPs will provide insight into the IGF-independent actions of the classical high affinity IGFBPs and their impact on cancer cell growth.