IGFBP-6 is an O-linked glycoprotein that binds IGF-II with marked preferential affinity over IGF-I . The protein prolongs the half-life of IGFs and can either inhibit or stimulate their growth-promoting effects on cell culture . It alters the interaction of IGFs with their cell surface receptors, thereby modulating their biological activity . IGFBP-6 is involved in various cellular processes, including cell migration and the positive regulation of the stress-activated MAPK cascade .
Recombinant human IGFBP-6 (rhIGFBP-6) is synthesized using eukaryotic expression systems, such as COS-7 monkey kidney cells . This recombinant form is similar to IGFBP-6 purified from human cerebrospinal fluid in terms of IGF binding and O-glycosylation . The recombinant protein has been used in various studies to understand its role in cellular differentiation and its interaction with IGFs.
IGFBP-6 has been shown to inhibit IGF-II-induced differentiation of L6A1 myoblasts in a dose-dependent manner . This inhibition is complete when rhIGFBP-6 is present in a slight molar excess. In contrast, rhIGFBP-6 does not affect IGF-I-induced differentiation, even when present in a five-fold molar excess . These findings highlight the specificity of IGFBP-6 for IGF-II and its potential role in regulating IGF-II-mediated cellular processes.
IGFBP-6 is implicated in various diseases and conditions. It is a biomarker for breast cancer, in situ carcinoma, leiomyoma, and neovascular inflammatory vitreoretinopathy . Additionally, it is involved in obesity and has been studied for its role in cell migration and the activation of the MAPK signaling pathway .