Baier T G, Jenne E W, Blum W, Schönberg D, Hartmann K K
Department of Pediatrics, University of Heidelberg, F.R.G.
Leuk Res. 1992 Aug;16(8):807-14. doi: 10.1016/0145-2126(92)90160-9.
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.
为了评估胰岛素样生长因子-I（IGF-I）和胰岛素作为生长促进因子在恶性淋巴细胞发育中的潜在作用，我们检测了分化阶段逐渐增加的成熟T急性淋巴细胞白血病（ALL）细胞系HSB2、HUT78、CEM、MOLT3、Jurkat、JM-P、JM-886，以及4种成熟的前B-ALL和B-ALL细胞系REH、SKW6、CESS，检测它们IGF-I的产生情况，以及在存在针对IGF-I或胰岛素或其受体的抗体时的生长情况。针对IGF-I的单克隆抗体（ASC41）和针对IGF-I受体的抗体（α-IR3）均能以剂量依赖的方式抑制早期分化的T细胞系HSB2和HUT78以及B细胞系REH的基础DNA合成，这表明IGF-I通过IGF-I受体作为这些细胞的自分泌或旁分泌生长因子。HUT78和REH从这些细胞中分泌IGF-I到细胞培养基中。α-IR3以及针对胰岛素受体（RPN.538）和胰岛素（RPN.1661）的抗体可抑制进一步分化的T细胞系CEM和MOLT3的DNA合成。这些结果表明，胰岛素通过IGF-I受体或胰岛素受体可作为这些T-ALL中的自分泌或旁分泌生长因子。最分化的T-ALL Jurkat和JMP的增殖仅被α-IR3和针对IGF-II受体的抗体2C2抑制，这表明通过IGF-I受体或IGF-II受体起作用的IGF-I或IGF-II可能参与这些细胞系的增殖。RPN.538和RPN.1661对DNA合成的抑制表明胰岛素在B-ALL细胞系SKW6和CESS白血病生长中起更重要的作用。
