Influence of antibodies against IGF-I, insulin or their receptors on proliferation of human acute lymphoblastic leukemia cell lines

Abstract

To evaluate the potential role of IGF-I and insulin as growth-promoting factors in malignant lymphocyte development, we examined established T-acute lymphoblastic leukemic (ALL) cell lines with increasing stage of differentiation, HSB2, HUT78, CEM, MOLT3, Jurkat, JM-P, JM-886, and four established preB- and B-ALL cell lines REH, SKW6 CESS, BJAB for production of IGF-I and growth in the presence of antibodies, directed against IGF-I or insulin or their receptors. Basal DNA synthesis of the early differentiated T-cell lines HSB2 and HUT78, as well as the B-cell line REH, could be inhibited in a dose-dependent manner by both monoclonal antibodies against IGF-I (ASC41) and antibodies against the IGF-I receptor (alpha-IR3), suggesting that IGF-I acts as an auto- or paracrine growth factor for these cells via the IGF-I receptor. From these cells HUT78 and REH secreted IGF-I into cell culture medium. DNA synthesis of the further differentiated T-cell lines CEM and MOLT3 was inhibited by alpha-IR3 and antibodies directed against the insulin receptor (RPN.538) and against insulin (RPN.1661). These results suggest that insulin via the IGF-I receptor or insulin receptor can function as an autocrine or paracrine growth factor in these T-ALLs. Proliferation of the most differentiated T-ALL Jurkat and JMP was inhibited only by alpha-IR3 and 2C2, an antibody directed against the IGF-II receptor, suggesting that IGF-I or IGF-II acting via the IGF-I receptor or IGF-II receptor may be involved in proliferation of these cell lines. Inhibition of the DNA synthesis by RPN.538 and RPN.1661 indicate a more important role for insulin in growth of leukemias of the B-ALL cell lines SKW6 and CESS.