Head neck squamous cell carcinoma c-Met+ cells display cancer stem cell properties and are responsible for cisplatin-resistance and metastasis
Head neck squamous cell carcinoma c-Met+ cells display cancer stem cell properties and are responsible for cisplatin-resistance and metastasis
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DOI：
10.1002/ijc.25927
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发表时间：
2011-11-15
影响因子：
6.4
通讯作者：
Wang, Zuolin
中科院分区：
文献类型：
--
作者：
Sun, Shuyang;Wang, Zuolin
c-Met 是肝细胞生长因子的酪氨酸激酶受体，在多种肿瘤中过度表达，在恶性转化中发挥核心作用。尽管 c-Met 也已被确定为正常干细胞功能中的关键信号分子，但 c-Met 作为癌症干细胞 (CSC) 单一标记物的潜在作用此前尚未得到研究。在我们的研究中，我们报道了表达c-Met的人头颈鳞状细胞癌（HNSCC）细胞能够自我更新并产生重现亲本肿瘤异质性的肿瘤，并且使用第二标记物CD44分离HNSCC细胞可以进一步增强体内致瘤性。我们还报道，c-Met(+) HNSCC 细胞可以在非贴壁培养条件下轻松形成球形集落，相比之下，c-Met(-) 群体则不然；这些球形集落可以传代多次而不会丧失集落形成能力。此外，我们发现c-Met(+) HNSCC细胞的自我更新途径表达增加，顺铂治疗不会影响这些途径，并负责介导转移。这些结果表明，c-Met 至少在 HNSCC 中可以作为 CSC 的新标志物，并且 c-Met(+) HNSCC 群体的高度化疗和转移能力使其成为更好地定义和理解其功能的重要细胞类型。
c-Met, the tyrosine kinase receptor for hepatocyte growth factor, is overexpressed in a variety of tumors in which it plays a central role in malignant transformation. Although c-Met has also been determined to be a critical signaling molecule in normal stem cell function, the potential role of c-Met as a single marker for cancer stem cells (CSCs) has not been previously examined. In our study, we reported that human head neck squamous cell carcinoma (HNSCC) cells expressing c-Met were capable of self-renewal and of generating tumors that recapitulate the heterogeneity of the parental tumors, and isolation of HNSCC cells using a second marker CD44 could further enhance upon the in-vivo tumorigenicity. We also reported that c-Met(+) HNSCC cells could readily make spherical colonies in nonadherent culture conditions, in contrast, c-Met(-) population did not; these spherical colonies could be passaged multiple times without loss of colony-forming capability. Furthermore, we showed that c-Met(+) HNSCC cells have increased expression of self-renewal pathways are spared by cisplatin treatment and are responsible for mediating metastasis. These results indicated that c-Met could serve as a novel marker for CSCs at least in HNSCC, and the highly chemoresistant and metastatic capabilities of c-Met(+) HNSCC population make them an important cell type to better define and understand their function.