Pepe M G, Ginzton N H, Lee P D, Hintz R L, Greenberg P L
Department of Medicine, Stanford University Medical Center, Palo Alto, California 94304.
J Cell Physiol. 1987 Nov;133(2):219-27. doi: 10.1002/jcp.1041330204.
Insulin and insulinlike growth factors I and II (IGF-I and IGF-II) influence mesodermal cell proliferation and differentiation. As multiple growth factors are involved in hemopoietic cell proliferation and differentiation, we assessed the receptor binding and mitogenic effects of these peptides on a panel of mesodermally derived human myeloid leukemic cell lines. The promyelocytic cell line HL60 had the highest level of specific binding for these 125I-labeled ligands, with lower binding to the less differentiated myeloblast cell line KG1 and undifferentiated blast variants of these cell lines (HL60blast, KG1a). Insulin binding affinity and receptor numbers were reduced significantly by chemically induced granulocytic differentiation of HL60 cells and was unchanged following induced monocytic differentiation. No substantial alteration in IGF-I or -II binding occurred with induced HL60 cell differentiation. Insulin and IGF-I demonstrated cross competition for receptor binding and down-regulated their homologous receptors without detectable cross modulation of the heterologous receptors on HL60 cells. IGF-I and insulin increased HL60 cell proliferation, as assessed by 3H-thymidine uptake, IGF-I greater than insulin. IGF-I binding and mitogenic effects were blocked by the monoclonal anti-IGF-I receptor antibody IR3, indicating that IGF-I-induced proliferative effects were mediated via its homologous receptor. In contrast, insulin binding and mitogenesis displayed blocking by both anti-IGI-I and anti-insulin receptor antibodies, indicating mediation of its activity through both receptors. These data demonstrate specific binding and mitogenic interactions between insulin, IGFs, and hemopoietic cells which are associated with their state of differentiation.
胰岛素以及胰岛素样生长因子I和II（IGF-I和IGF-II）会影响中胚层细胞的增殖和分化。由于多种生长因子参与造血细胞的增殖和分化，我们评估了这些肽对一组中胚层来源的人类髓系白血病细胞系的受体结合及促有丝分裂作用。早幼粒细胞系HL60对这些125I标记配体的特异性结合水平最高，与分化程度较低的成髓细胞系KG1及其这些细胞系的未分化原始细胞变体（HL60blast、KG1a）的结合较低。HL60细胞经化学诱导粒细胞分化后，胰岛素结合亲和力和受体数量显著降低，而诱导单核细胞分化后则无变化。HL60细胞诱导分化后，IGF-I或-II的结合未发生实质性改变。胰岛素和IGF-I在受体结合上表现出交叉竞争，并下调其同源受体，而对HL60细胞上的异源受体无明显交叉调节作用。通过3H-胸腺嘧啶核苷摄取评估，IGF-I和胰岛素可增加HL60细胞增殖，IGF-I的作用大于胰岛素。IGF-I的结合及促有丝分裂作用被单克隆抗IGF-I受体抗体IR3阻断，表明IGF-I诱导的增殖作用是通过其同源受体介导的。相反，胰岛素的结合及促有丝分裂作用被抗IGF-I和抗胰岛素受体抗体均阻断，表明其活性是通过这两种受体介导的。这些数据证明了胰岛素、IGF与造血细胞之间存在与它们分化状态相关的特异性结合及促有丝分裂相互作用。
