Soluble insulin-like growth factor II/mannose 6-phosphate receptor inhibits DNA synthesis in insulin-like growth factor II sensitive cells

✍ Scribed by Carolyn D. Scott; Jocelyn Weiss

• Publisher: John Wiley and Sons
• Year: 2000
• Tongue: English
• Weight: 172 KB
• Volume: 182
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/(sici)1097-4652(200001)182:1<62::aid-jcp7>3.0.co;2-x

✦ Synopsis

The soluble form of the insulin-like growth factor II (IGF-II)/mannose 6-P (IGF-II/ M6P) receptor is released by cells in culture and circulates in the serum. It retains its ability to bind IGF-II and blocks IGF-II-stimulated DNA synthesis in isolated rat hepatocytes. Because these cells are not normally stimulated to divide by IGF-II in vivo, the effect of soluble IGF-II/M6P receptor on DNA synthesis has been further investigated in two cell lines sensitive to IGF-II; mouse 3T3(A31) fibroblasts, stimulated by low levels of IGF-II following priming by epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) and Buffalo rat liver (BRL) cells, which secrete IGF-II and proliferate in the absence of exogenous growth factors. Soluble IGF-II/M6P receptor (0.2-2.0 g/ml) purified from a rat hepatoma cell line inhibited DNA synthesis (determined by dThd incorporation) in both cell lines. Basal DNA synthesis was very low in serum-free 3T3 cells, but high in serum-free BRL cells, possibly as a result of autocrine IGF-II production. The inhibitory effect was reversible in cells preincubated with soluble receptor prior to incubation with growth factors and could also be overcome by excess IGF-II. Soluble receptor was more potent in IGF-II-stimulated 3T3 cells and serum-free BRL cells than in BRL cells incubated with serum. Mean inhibition by four preparations of soluble receptor (1 g/ml) was 34.7% Ϯ 4.4% in BRL cells stimulated with fetal calf serum (FCS) (5%) compared to 54.8% Ϯ 4.2% in serum-free BRL cells (P ϭ 0.05) and 60.6% Ϯ 6.5% (P ϭ 0.02) in 3T3 cells stimulated by PDGF, EGF, and IGF-II. Soluble receptor had no effect on DNA synthesis in 3T3 cells stimulated with IGF-I. These results demonstrate that soluble receptor, at physiological concentrations, can block proliferation of cells by IGF-II and could therefore play a role in blocking tumor growth mediated by IGF-II.