Premium
Soluble insulin‐like growth factor II/mannose 6‐phosphate receptor inhibits DNA synthesis in insulin‐like growth factor II sensitive cells
Author(s) -
Scott Carolyn D.,
Weiss Jocelyn
Publication year - 2000
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/(sici)1097-4652(200001)182:1<62::aid-jcp7>3.0.co;2-x
Subject(s) - dna synthesis , growth factor , biology , receptor , epidermal growth factor , cell culture , autocrine signalling , insulin like growth factor , insulin like growth factor receptor , mannose , microbiology and biotechnology , endocrinology , medicine , biochemistry , in vitro , genetics
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 μg/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 μg/ml) was 34.7% ± 4.4% in BRL cells stimulated with fetal calf serum (FCS) (5%) compared to 54.8% ± 4.2% in serum‐free BRL cells (P = 0.05) and 60.6% ± 6.5% (P = 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. J. Cell. Physiol. 182:62–68, 2000. © 2000 Wiley‐Liss, Inc.