Insulin-like growth factor binding protein-6 inhibits neuroblastoma cell proliferation and tumour development

Promotion of Cancer Cell Migration

“…One study proposed IGF-independent effects of IGFBP-6 in neuroblastoma cells based on its similar effects in the presence and absence of IGFs and des-(1-3)IGF-I, to which it does not bind (17). However, another study by the same group did not confirm this finding (18). In osteoblasts, antisense suppression of IGFBP-6 decreased basal levels of alkaline phosphatase, a differentiation marker (20).…”

“…Because of its binding preference, IGFBP-6 inhibits IGF-II-induced cell proliferation, differentiation, and survival (12)(13)(14)(15)(16), but it has marginal or no effect on IGF-I actions. A few studies have suggested that IGFBP-6 may have IGF-independent effects, but they have not been definitively demonstrated (17)(18)(19)(20). In this study, we have generated a non-IGF-binding IGFBP-6 mutant (mIGFBP-6) and used it as a tool to study possible IGF-independent effects of IGFBP-6.…”

IGFBP-6 five years on; not so ‘forgotten’?

“…Des(1-3)IGF-I does not bind to IGFBP-6, so it appears that this IGFBP-6 effect was not due to sequestration of IGFs. Interestingly, a subsequent study by the same group showed that addition of exogenous IGFBP-6 did not inhibit des(1-3)IGF-I-induced thymidine incorporation in the same cells [12]. Taken together, these results might indicate that the effects seen in the first study were due to clonal differences, or that IGFBP-6 needs to be endogenously synthesized to exert IGF-independent effects.…”

“…Further, infusion of IGFBP-6 also delayed neuroblastoma xenograft growth in vivo, probably by inhibiting IGF-II actions [12]. Overexpression of the N-myc oncogene, which is associated with poor prognosis in neuroblastoma, decreased IGFBP-6 and increased IGFBP-2 and IGF-I receptor levels [13].…”

Transcriptional activation of insulin-like growth factor binding protein 6 by 17β-estradiol in SaOS-2 cells

“…Generally, IGFBPs play an IGF-dependent role in high affinity IGF binding. Some studies have suggested that IGFBP-6 has IGF-independent effects (Grellier et al, 1998;Seurin et al, 2002;. Among the IGFBPs, IGFBP-6 is unique in stimulation of osteosarcoma cell growth and has an anti-apoptotic effect (Schmid et al, 1999).…”