Stevens R L, Austen K F, Nissley S P
J Biol Chem. 1983 Mar 10;258(5):2940-4.
125I-Insulin binding to rat chondrosarcoma chondrocytes increased, rather than decreased, when these transformed cells were maintained for 1-8 days in primary culture with incremental concentrations of insulin (3 to 1000 ng/ml). The increase in 125I-insulin binding was reversible and depended on the concentration of insulin in which the cells had been previously cultured. The chondrocytes did not change their phenotype in response to the incremental insulin concentrations in the culture medium. The variations in binding of radioligand were not due to different rates of internalization of the ligand-receptor complex, to protease degradation of the radioligand, to shedding of the insulin receptor, or to secretion of an inhibitory insulin binding component. Scatchard analyses of 125I-insulin binding data indicated the induction of a high affinity insulin receptor in the cells cultured in the presence of insulin. The insulin-induced increase in 125I-insulin binding was not associated with an increase in the binding of 125I-labeled multiplication-stimulating activity (125I-MSA), an insulin-like growth factor. Conversely, culturing the chondrocytes in 0.1-1.0 micrograms/ml of MSA did not alter the subsequent binding of either 125I-MSA or 125I-insulin. The insulin-induced increase in insulin binding to these transformed cells may be an abnormality in metabolic control that facilitates growth of the tumor in vivo.
当这些转化细胞在原代培养中用递增浓度的胰岛素(3至1000纳克/毫升)维持1至8天时,125I-胰岛素与大鼠软骨肉瘤软骨细胞的结合增加而非减少。125I-胰岛素结合的增加是可逆的,并且取决于细胞先前培养时胰岛素的浓度。软骨细胞不会因培养基中递增的胰岛素浓度而改变其表型。放射性配体结合的变化并非由于配体-受体复合物内化速率不同、放射性配体的蛋白酶降解、胰岛素受体的脱落或抑制性胰岛素结合成分的分泌。对125I-胰岛素结合数据的Scatchard分析表明,在胰岛素存在下培养的细胞中诱导出了高亲和力胰岛素受体。胰岛素诱导的125I-胰岛素结合增加与125I标记的促增殖活性(125I-MSA)(一种胰岛素样生长因子)的结合增加无关。相反,将软骨细胞培养在0.1至1.0微克/毫升的MSA中不会改变随后125I-MSA或125I-胰岛素的结合。胰岛素诱导的这些转化细胞胰岛素结合增加可能是代谢控制中的一种异常,它促进了肿瘤在体内的生长。