Common pathway for tumor cell uptake of gallium-67 and iron-59 via a transferrin receptor.

Common pathway for tumor cell uptake of gallium-67 and iron-59 via a transferrin receptor.
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肿瘤细胞通过转铁蛋白受体摄取镓 67 和铁 59 的常见途径。

DOI:
10.1093/jnci/64.1.41
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发表时间:
1980
期刊:
Journal of the National Cancer Institute
影响因子:
--
通讯作者:
D. L. Williams
D. L. Williams
中科院分区:
--
文献类型:
--
作者:
S. Larson;J. Rasey;D. Allen;N. Nelson;Z. Grunbaum;G. Harp;D. L. Williams

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我们研究了[67 Ga]柠檬酸盐、[59 Fe]柠檬酸盐和125 I标记的转铁蛋白(TF)在体外生长形式的EMT-6(BALB/c小鼠的肉瘤样乳腺肿瘤)的肿瘤摄取。在分析结合实验中,我们开发了一种新的数学模型,该模型基于最初用于表达激素与特定组织受体相互作用的配方。肿瘤细胞对无载体67 Ga和59 Fe的摄取由动力学相同的TF受体介导。我们还研究了在体内和体外生长的EMT-6肿瘤的基质的特黄酸提取物。这些提取物在Sephacryl S-200 SF上的色谱分析表明,细胞基质中含有特异性TF结合大分子。在此基础上,我们提出了肿瘤摄取67 Ga机制的“转铁蛋白受体假说”。根据这种观点,肿瘤相关TF受体是负责镓对某些肿瘤的亲和力的功能单位。这种受体在肿瘤对铁的摄取中也是活跃的。
We studied the tumor uptake of [67Ga]citrate, [59Fe]citrate, and 125I-labeled transferrin (TF) by the in vitro growth form of EMT-6, a sarcoma-like mammary tumor of BALB/c mice. In analyzing the binding experiments, we developed a new mathematical model based on a formulation originally used to express the interaction of hormones with specific tissue receptors. The uptake of both carrier-free 67Ga and 59Fe by tumor cells was mediated by kinetically identical TF receptors. We also studied teric acid extracts of the stroma of EMT-6 tumors grown both in vivo and in vitro. Chromatography of these extracts on Sephacryl S-200 SF demonstrated that the cellular stroma contained specific TF-binding macromolecules. On the basis of these findings, we proposed the "transferrin receptor hypothesis" for the mechanism of 67Ga uptake by tumors. According to this view, a tumor-associated TF receptor is the functional unit responsible for the affinity of gallium for certain neoplasms. This receptor was also active in the uptake of iron by tumors.