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

Abstract

In neuroblastoma cells, survival and proliferation are dependent upon the insulin-like growth factor (IGF) system. IGFs actively participate in cell growth, whereas IGFBP-6, is associated with the arrest of growth. With a view to blocking IGF-II action, we produced recombinant human IGFBP-6 capable of binding IGFs with affinities between 1.23 and 6.36 x 10(9) M(-1). Ex vivo mitogenic activities were tested on two human neuroblastoma cell lines, in which 100 ng/ml IGFBP-6 completely abolished the effects of both endogenous and exogenous IGF-II. In vivo, nude mice previously injected with neuroblastoma cells were submitted to either 15 daily injections of 4-20 microg IGFBP-6 or implantation of mini-pumps diffusing 20-100 microg IGFBP-6 over 2 weeks. The result was an average 18% reduction in the incidence and development of tumours. Delivery of the IGFBP-6 via mini-pumps also delayed tumour appearance by 6-15 days. Our results therefore show the involvement of IGFBP-6 in neuroblastoma cell growth, both ex vivo in terms of proliferation and in vivo in terms of tumour development.

• Authors: D Seurin, C Lassarre, G Bienvenu, S Babajko
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 38 Issue 15 Pg. 2058-65 (Oct 2002) ISSN: 0959-8049 [Print] England
• PMID: 12376212 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Insulin-Like Growth Factor Binding Protein 6
• Insulin-Like Growth Factor II

Topics

• Animals
• Cell Division
• Female
• Humans
• Insulin-Like Growth Factor Binding Protein 6 (therapeutic use)
• Insulin-Like Growth Factor II (antagonists & inhibitors)
• Mice
• Mice, Nude
• Neoplasm Transplantation
• Neuroblastoma (drug therapy, pathology)
• Tumor Cells, Cultured