ABCB1 identifies a subpopulation of uveal melanoma cells with high metastatic propensity.

ABCB1 identifies a subpopulation of uveal melanoma cells with high metastatic propensity.
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DOI:
10.1111/j.1755-148x.2011.00841.x
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发表时间:
2011-06
影响因子:
4.3
通讯作者:
Harbour JW
Harbour JW
中科院分区:
医学3区
文献类型:
--
作者:
Landreville S;Agapova OA;Kneass ZT;Salesse C;Harbour JW

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肿瘤细胞向远处器官转移是黑色素瘤死亡的主要原因。然而,转移的机制仍然知之甚少。一个关键问题是原发肿瘤中的所有细胞是否都有同样的转移可能性,还是亚群细胞优先引起转移。在这里,我们发现了一个表达多药耐药转运体ABCB1的葡萄膜黑色素瘤细胞亚群,与ABCB1 -大块肿瘤细胞相比,它们具有高度转移性。与ABCB1−细胞相比,ABCB1+细胞还表现出增强的克隆原性、锚定独立生长、致瘤性和线粒体活性。A375皮肤黑色素瘤细胞含有类似的高转移性ABCB1+细胞亚群。这些发现表明,一些葡萄膜黑色素瘤细胞比其他细胞有更大的转移潜力,更好地了解这些细胞可能是治疗转移性黑色素瘤更成功的必要条件。
Metastasis of tumor cells to distant organs is the leading cause of death in melanoma. Yet, the mechanisms of metastasis remain poorly understood. One key question is whether all cells in a primary tumor are equally likely to metastasize or whether subpopulations of cells preferentially give rise to metastases. Here, we identified a subpopulation of uveal melanoma cells expressing the multidrug resistance transporter ABCB1 that are highly metastatic compared to ABCB1− bulk tumor cells. ABCB1+ cells also exhibited enhanced clonogenicity, anchorage independent growth, tumorigenicity and mitochondrial activity compared to ABCB1− cells. A375 cutaneous melanoma cells contained a similar subpopulation of highly metastatic ABCB1+ cells. These findings suggest that some uveal melanoma cells have greater potential for metastasis than others, and that a better understanding of such cells may be necessary for more successful therapies for metastatic melanoma.