Head neck squamous cell carcinoma c-Met+ cells display cancer stem cell properties and are responsible for cisplatin-resistance and metastasis

Authors

  • Shuyang Sun,

    1. Department of Oral and Maxillofacial Surgery, School of Stomatology, Tongji University, Shanghai, China
    2. College of Life Science and Technology, Tongji University, Shanghai, China
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  • Zuolin Wang

    Corresponding author
    1. Department of Oral and Maxillofacial Surgery, School of Stomatology, Tongji University, Shanghai, China
    • Department of Oral and Maxillofacial Surgery, Tongji University, No. 399, Yan Chang Middle Road, Shanghai, 200072, China
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    • Tel.: 86-21-66524025, Fax: 86-21-66524025


Abstract

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.

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