Chitambar C R, Zivkovic Z
Cancer Res. 1987 Aug 1;47(15):3929-34.
We have studied the role of transferrin and the transferrin receptor in the uptake of 67Ga by the human leukemic cell line HL60. In the absence of transferrin, HL60 cells incorporated about 1% of the 67Ga dose over 6 h. The presence of transferrin increased cellular 67Ga uptake approximately 10-fold. Transferrin-mediated uptake of 67Ga was blocked by an anti-transferrin receptor monoclonal antibody, and decreases in the density of cellular transferrin receptors led to corresponding decreases in the transferrin-dependent uptake of 67Ga. Changes in the cellular ferritin content did not significantly influence the uptake of 67Ga by either transferrin-independent or transferrin-dependent pathways. Regardless of the mechanism of uptake, a significant amount of intracellular 67Ga was found to be associated with immunoprecipitable ferritin as well as with a free pool. This free intracellular 67Ga appeared to be kinetically active since cells released 67Ga back to the media over time. Our results demonstrate the existence of a dual mechanism for the cellular uptake of 67Ga and suggest that the preferential uptake of 67Ga by lymphomas is related to the high density of transferrin receptors known to be expressed by these tumors in vivo.
我们研究了转铁蛋白和转铁蛋白受体在人白血病细胞系HL60摄取67Ga中的作用。在没有转铁蛋白的情况下，HL60细胞在6小时内摄取了约1%的67Ga剂量。转铁蛋白的存在使细胞对67Ga的摄取增加了约10倍。转铁蛋白介导的67Ga摄取被抗转铁蛋白受体单克隆抗体阻断，细胞转铁蛋白受体密度的降低导致转铁蛋白依赖性67Ga摄取相应减少。细胞铁蛋白含量的变化对非转铁蛋白依赖性或转铁蛋白依赖性途径摄取67Ga均无显著影响。无论摄取机制如何，发现大量细胞内67Ga与可免疫沉淀的铁蛋白以及游离池相关。这种细胞内游离67Ga似乎具有动力学活性，因为随着时间的推移细胞会将67Ga释放回培养基中。我们的结果证明了细胞摄取67Ga存在双重机制，并表明淋巴瘤对67Ga的优先摄取与这些肿瘤在体内已知表达的高密度转铁蛋白受体有关。
