Membrane-associated Insulin-like Growth Factor-binding Protein-3 Inhibits Insulin-like Growth Factor-I-induced Insulin-like Growth Factor-I Receptor Signaling in Ishikawa Endometrial Cancer Cells

Insulin-Like Growth Factor Binding Protein-3 Interacts with Autocrine Motility Factor/Phosphoglucose Isomerase (AMF/PGI) and Inhibits the AMF/PGI Function

“…Conformational changes in IGFBP-3 after binding to IGF-I have been shown to enhance the binding of IGFBP-3 to the acid-labile subunit (26), and a similar mechanism may explain the enhanced potency of the binary complex to inhibit AMF/PGI catalytic activity. However, we have previously shown that IGF-I inhibits the binding of IGFBP-3 to T47D cells (14), an observation that is consistent with reports in other cell lines (8,9,27). Furthermore, in the presence of IGF-I, we are unable to cross-link IGFBP-3 to AMF/PGI, and the M r ϳ80,000 complex that represents IGFBP-3/AMF/PGI is not observed (14).…”

Transforming growth factor-beta induces growth inhibition and IGF-binding protein-3 production in prostatic stromal cells: abnormalities in cells cultured from benign prostatic hyperplasia tissues

“…The hypothesis commonly proposed regarding this highly regulated IGFBP secretion from cells is that local IGFBP levels govern the proliferation and survival of the cells by regulating the levels of free autocrine IGFs available to interact with the IGF receptor. Alternatively, we and others proposed that the levels of IGFBPs, particularly IGFBP-3, directly regulate cell growth and death via the recently proposed IGFBP-3 receptors/association proteins (Conover 1992, Cohen et al 1993, Oh et al 1993a, Valentinis et al 1995, Angelloz-Nicoud et al 1996, Gucev et al 1996, Lalou et al 1996, Neuenschwander et al 1996, Gill et al 1997, Karas et al 1997, Leal et al 1997, Mohseni-Zadeh & Binoux 1997, Rechler 1997.…”

“…6, bind IGFBP-3 specifically, and with high affinity (Oh et al 1993b). IGFBP-3 may also bind an additional molecules including the type V TGF-receptor, matrix and cell surface structures, or the IGF-1 receptor (Karas et al 1997, Leal et al 1997, Mohseni-Zadeh & Binoux 1997.…”

“…Using a breast cancer model, Oh et al (1995) demonstrated that the stimulation of IGFBP-3 by TGF-2 is critical to TGF--induced growth inhibition, and Rajah et al (1997) showed that IGFBP-3 expression is necessary for TGF-1-induced apoptosis in a prostate cancer model. Several investigators suggest that IGFBP-3 acts directly through binding to specific cell surface receptors on susceptible cells (Conover 1992, Cohen et al 1993, Oh et al 1993a, Valentinis et al 1995, Angelloz-Nicoud et al 1996, Gucev et al 1996, Lalou et al 1996, Neuenschwander et al 1996, Gill et al 1997, Karas et al 1997, Leal et al 1997, Mohseni-Zadeh & Binoux 1997, Rechler 1997.…”

Cancer

“…Because the binding affinity of IGF for the IGFBPs exceeds that for IGF-1R, IGFBPs tend to reduce IGF/IGF-1R signaling through competitive binding. This has been demonstrated by numerous experiments in different cell types using Des-(l-3)-IGF-I, an IGF-I analog that binds IGF-1R and stimulates DNA synthesis but cannot bind IGFBP-3 [107][108][109] As the principai endocrine IGFBP, IGFBP-3 is the best studied and will be the focus of this discussion.…”