Departments of Ophthalmology and Visual Sciences, Washington University School of Medicine, St Louis, MO, USA. Département d'Ophtalmologie, Université Laval, Québec, QC, Canada Department of Otolaryngology, Washington University School of Medicine, St Louis, MO, USA.
Pigment Cell Melanoma Res. 2011 Jun;24(3):430-7. doi: 10.1111/j.1755-148X.2011.00841.x. Epub 2011 Mar 24.
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.
肿瘤细胞转移到远处器官是黑色素瘤死亡的主要原因。然而，转移的机制仍知之甚少。一个关键问题是，原发性肿瘤中的所有细胞是否都具有同等的转移可能性，还是细胞的亚群优先形成转移。在这里，我们鉴定出一群表达多药耐药转运蛋白 ABCB1 的葡萄膜黑色素瘤细胞，与 ABCB1(-) 肿瘤细胞相比，这些细胞具有高度的转移性。与 ABCB1(-) 细胞相比，ABCB1(+) 细胞还表现出增强的集落形成能力、非锚定依赖性生长、致瘤性和线粒体活性。A375 皮肤黑色素瘤细胞中也存在类似的具有高转移性的 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具有更大的转移潜力，因此，为了更成功地治疗转移性黑色素瘤，可能需要更好地了解这些细胞。
