Insulin-like growth factor binding protein-6 inhibits neuroblastoma cell proliferation and tumour development.
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.
Seurin
D
D
Unit de Recherches sur la Regulation de la Croissance, U. 515, Institut National de la Santé et de la Recherche Médicale, Hôpital Saint Antoine, 184, rue du Faubourg Saint Antoine, 75571 Paris Cedex 12, France.
Lassarre
C
C
Bienvenu
G
G
Babajko
S
S
D000818:Animals; D002455:Cell Division; D005260:Female; D006801:Humans; D018976:Insulin-Like Growth Factor Binding Protein 6 / Q000627:therapeutic use*; D007335:Insulin-Like Growth Factor II / Q000037:antagonists & inhibitors*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009447:Neuroblastoma / Q000188:drug therapy / Q000473:pathology*; D014407:Tumor Cells, Cultured
D018976:Insulin-Like Growth Factor Binding Protein 6; D007335:Insulin-Like Growth Factor II