Characterization of melanoma cells capable of propagating tumors from a single cell.
Characterization of melanoma cells capable of propagating tumors from a single cell.
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DOI：
10.1158/0008-5472.can-09-2153
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发表时间：
2010-01-01
期刊：
影响因子：
11.2
通讯作者：
Bosenberg MW
中科院分区：
文献类型：
--
作者：
Held MA;Curley DP;Dankort D;McMahon M;Muthusamy V;Bosenberg MW
在包括黑色素瘤在内的不同类型的癌症中，具有肿瘤增殖能力的细胞的性质和数量仍然存在疑问。在某种程度上，这是因为迄今为止尚未实现纯化的致瘤性癌细胞亚群的鉴定和表征。在这里，我们报告了在注射来自三种新型小鼠模型的单一纯化黑色素瘤细胞后形成的肿瘤。每次注射单个CD34+p75−黑色素瘤细胞后都发生肿瘤形成，使用CD34−p75−细胞的发生率中等，而使用CD34−p75−细胞的发生率很少。这些发现表明，致瘤性黑色素瘤细胞可能比以前认为的更常见，并确定在单个肿瘤中可以存在多个不同的黑色素瘤繁殖细胞（MPC）群。有趣的是，单个CD34−p75−MPCs在小鼠体内或体外多次传代形成肿瘤后可以再生细胞异质性，而CD34+p75−MPCs仅进行自我更新，这表明肿瘤异质性的重建并不总是能够形成肿瘤的单个细胞的特征。功能上，单一纯化的MPCs比非MPCs更耐化疗。我们期望这些MPCs的纯化可以更全面地评估黑色素瘤中定义肿瘤形成能力和化疗耐药性的分子特征。
Questions persist about the nature and number of cells with tumor-propagating capability in different types of cancer, including melanoma. In part, this is because identification and characterization of purified tumorigenic subsets of cancer cells has not been achieved to date. Here, we report tumor formation after injection of single purified melanoma cells derived from three novel mouse models. Tumor formation occurred after every injection of individual CD34+p75− melanoma cells, with intermediate rates using CD34−p75− cells, and rarely with CD34−p75+ cells. These findings suggest that tumorigenic melanoma cells may be more common than previously thought and establish that multiple distinct populations of melanoma-propagating cells (MPC) can exist within a single tumor. Interestingly, individual CD34−p75− MPCs could regenerate cellular heterogeneity after tumor formation in mice or multiple passages in vitro, whereas CD34+p75− MPCs underwent self-renewal only, showing that reestablishment of tumor heterogeneity is not always a characteristic of individual cells capable of forming tumors. Functionally, single purified MPCs were more resistant to chemotherapy than non-MPCs. We anticipate that purification of these MPCs may allow a more comprehensive evaluation of the molecular features that define tumor-forming capability and chemotherapeutic resistance in melanoma.