IGFBPs are involved in xenograft development in nude mice.

Abstract

BACKGROUND:

The insulin-like growth factors (IGFs) are involved in the growth and differentiation of neuroblastoma cells. In all biological fluids, they are non-covalently bound to high-affinity binding proteins (IGFBP-1 to -6) which modulate their bioavailability. We previously showed that IGFBP-6 expression 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 plasmid containing sequences coding for IGFBP-6 under the control of the cytomegalovirus (CMV) promoter.

RESULTS:

The incidence and size of tumors generated by injecting IGFBP-6-expressing cells into nude mice were reduced by factors of 2 and 5, respectively, as compared with those generated by injection by control cells. Northern blot analyses if xenografts revealed weaker expression of IGF-II, type 2 IGF receptor and IGFBP-2 mRNAs in IGFBP-6-expressing cthan in control xenografts. IGFBP-6 may therefore reduce the expression of IGF-II (which induces tumour development) at a transcriptional level. Conversely, containing IGFBP-2 cDNA under the control of CMV promoter grew three to four times as fast as normal control xenografts. Northern blot analyses revealed weaker expression of intact IGFBP-3 and IGFBP-1 in IGFBP-2-expressing than in control xenografts.

CONCLUSIONS:

IGFBP-1 and intact IGFBP-3 expression both enhance IGF bioavailability which promotes tumour growth. Although the mechanisms of action of IGFBP-2 and IGFBP-6 remain to be elucidated, an inverse relationship appears to exist between the two binding proteins, IGFBP-2 being involved in proliferation and IGFBP-6 in its arrest.

• Authors: S Babajko, P Grellier, B de Gallé, M Menouny, M Binoux
• Journal: Medical and pediatric oncology (Med Pediatr Oncol) Vol. 36 Issue 1 Pg. 154-6 (Jan 2001) ISSN: 0098-1532 [Print] United States
• PMID: 11464872 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Insulin-Like Growth Factor Binding Protein 2
• Insulin-Like Growth Factor Binding Protein 6
• Insulin-Like Growth Factor Binding Proteins
• Recombinant Fusion Proteins
• Insulin-Like Growth Factor I
• Insulin-Like Growth Factor II

Topics

• Animals
• Biological Availability
• Cytomegalovirus (genetics)
• Genes, Synthetic
• Graft Survival
• Humans
• Insulin-Like Growth Factor Binding Protein 2 (genetics, physiology)
• Insulin-Like Growth Factor Binding Protein 6 (genetics, physiology)
• Insulin-Like Growth Factor Binding Proteins (physiology)
• Insulin-Like Growth Factor I (physiology)
• Insulin-Like Growth Factor II (physiology)
• KB Cells (metabolism, transplantation)
• Mice
• Mice, Nude
• Mitosis
• Neoplasm Transplantation (physiology)
• Neuroblastoma (pathology)
• Promoter Regions, Genetic
• Recombinant Fusion Proteins (physiology)
• Transfection
• Transgenes
• Transplantation, Heterologous (physiology)
• Tumor Cells, Cultured (metabolism, transplantation)