IGFBPs are involved in xenograft development in nude mice

Background. The insulin-like growth factors (IGFs) are involved in the grow th and differentiation of neuroblatoma cells, in all biological fluids, the y are non-covalently bound to high-affinity binding proteins (IGFBP-1 to -6 ) which modulate their bioavailability. We previously showed that IGFBP-6 e xpression is linked to the arrest of growth in neuroblastoma cells, whereas IGFBP-2 is associated with proliferation. Procedure. To study the role of IGFBP-6 in cell growth, we stably IGR-N-91 neuroblastoma cells with a plasm id containing sequences coding for IGFBP-6 under the control of the cytomeg alovirus (CMV) promoter. Results. The incidence and size of tumors generate d by injecting IGFBP-6-expressing cells into nude-mice were reduced by fact ors of 2 and 5, respectively, as compared with those generated by injection by control cells. Northern blot analyses if xenografts revealed weaker exp ression of IGF-II, type 2 IGF receptor and IGFBP-2 mRNAs in IGFBP-6-express ing than in control xenografts. IGFBP-6 may therefore reduce the expression of IGF-II (which induces tumour development) at a transcriptional level. C onversely, containing IGFBP-2 cDNA under the control of CMV promoter grew t hree to four times as fast as normal control xenografts. Northern blot anal yses revealed weaker expression of intact IGFBP-3 and IGFBP-1 in IGFBP-2-ex pressing than in control xenografts. Conclusions. IGFBP-1 and intact IGFBP- 3 expression both enhance ICF bioavailability which promotes tumour growth. Although the mechanisms of action of IGFBP-2 and IGFBP-6 remain to be eluc idated, an inverse relationship appears to exist between the two binding pr oteins, IGFBP-2 being involved in proliferation and IGFBP-6 in its arrest. Med. Pediatr. Oncol. 36:154-156, 2001. (C) 2001 Wiley-Liss. Inc.