IGFBP-6 is an O-linked glycoprotein that binds insulin-like growth factor-II (IGF-II) with a marked preferential affinity over IGF-I . This binding inhibits the activity of IGF-II, which is involved in various cellular processes such as proliferation, differentiation, and survival. IGFBP-6 has the strongest affinity for IGF-II among the IGFBPs, making it a critical regulator of IGF-II activity .
IGFBP-6 is synthesized in various tissues, including the central nervous system (CNS), and has been shown to inhibit proliferation in many cell types . It is involved in cell migration and the positive regulation of the stress-activated MAPK cascade . Additionally, IGFBP-6 has been implicated in obesity and other metabolic disorders .
Recombinant human IGFBP-6 (rhIGFBP-6) has been synthesized using COS-7 monkey kidney cells that were transiently transfected with a eukaryotic expression vector containing a complementary DNA for IGFBP-6 . This recombinant protein is similar to IGFBP-6 purified from human cerebrospinal fluid in terms of IGF binding and O-glycosylation .
Studies have shown that rhIGFBP-6 inhibits 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 preferential affinity of IGFBP-6 for IGF-II and its potential therapeutic applications in conditions where IGF-II activity needs to be modulated.
In the context of cancer research, IGFBP-6 has been shown to control the expansion of chemoresistant glioblastoma through paracrine IGF2/IGF-1R signaling . This suggests that IGFBP-6 could be a valuable target for developing new treatments for glioblastoma and other cancers.