Neely E K, Rosenfeld R G, Illescas A, Smith S D
Department of Pediatrics, Stanford University, California.
Leukemia. 1992 Nov;6(11):1134-42.
Insulin and the insulin-like growth factors (IGF-I, IGF-II) constitute a family of peptides capable of stimulating diverse cellular responses, including cell proliferation. In order to determine the effects of these peptides on malignant cells, we analyzed the expression and function of insulin, IGF-I, and IGF-II receptors on B-cell precursor acute lymphoblastic leukemia (BCP ALL) cell lines, utilizing competitive binding, affinity crosslinking, and cell proliferation assays. The BCP ALL cells bound to each peptide with mean specific binding for 125I-insulin, 125I-IGF-I, and 125I-IGF-II of 19.6%, 7.1%, and 4.3% of radioligand added, respectively. Competitive binding to intact cells demonstrated that 125I-IGF-I was displaced by IGF-I = IGF-II >> insulin, 125I-IGF-II was displaced by IGF-II > insulin = IGF-I, and 125I-insulin was displaced by insulin >> IGF-II > IGF-I. These data were remarkable for the potency of IGF-II displacement of 125I-IGF-I and 125I-insulin. Affinity crosslinking of radioligands to SUP-B2 cell membranes demonstrated the high affinity insulin and IGF-I (type 1 IGF) receptors. IGF binding proteins were also present in BCP ALL cell membrane preparations. In the cell proliferation studies, insulin stimulated a 50-130% increase in leukemic cell growth with a half-maximal concentration of 0.1-3.0 ng/ml in three BCP ALL cell lines. The proliferative response to insulin was blocked by the addition of an insulin receptor antibody. However, no response was observed with IGF-I, and IGF-II was only weakly mitogenic with a proliferative response noted at 100 ng/ml. Thus, while BCP ALL cells possess receptors for insulin and IGF-I, only the insulin receptor mediated a proliferative response.
胰岛素和胰岛素样生长因子（IGF-I、IGF-II）构成了一类能够刺激多种细胞反应（包括细胞增殖）的肽家族。为了确定这些肽对恶性细胞的影响，我们利用竞争性结合、亲和交联和细胞增殖试验，分析了胰岛素、IGF-I和IGF-II受体在B细胞前体急性淋巴细胞白血病（BCP ALL）细胞系中的表达和功能。BCP ALL细胞与每种肽结合，125I胰岛素、125I-IGF-I和125I-IGF-II的平均特异性结合分别为加入放射性配体的19.6%、7.1%和4.3%。对完整细胞的竞争性结合表明，125I-IGF-I被IGF-I = IGF-II >>胰岛素取代，125I-IGF-II被IGF-II >胰岛素 = IGF-I取代，125I胰岛素被胰岛素 >> IGF-II > IGF-I取代。这些数据因IGF-II对125I-IGF-I和125I胰岛素的置换效力而显著。放射性配体与SUP-B2细胞膜的亲和交联证明了高亲和力胰岛素和IGF-I（1型IGF）受体的存在。IGF结合蛋白也存在于BCP ALL细胞膜制剂中。在细胞增殖研究中，胰岛素刺激三种BCP ALL细胞系中的白血病细胞生长增加50 - 130%，半数最大浓度为0.1 - 3.0 ng/ml。加入胰岛素受体抗体可阻断对胰岛素的增殖反应。然而，未观察到IGF-I的反应，IGF-II只有微弱的促有丝分裂作用，在100 ng/ml时才有增殖反应。因此，虽然BCP ALL细胞具有胰岛素和IGF-I受体，但只有胰岛素受体介导了增殖反应。
