Journal
INTERNATIONAL JOURNAL OF CANCER
Volume 129, Issue 10, Pages 2337-2348Publisher
WILEY-BLACKWELL
DOI: 10.1002/ijc.25927
Keywords
c-Met; cancer stem cell marker; head neck squamous cell carcinoma; chemoresistance; metastasis
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Funding
- National Natural Science Foundation of China [30872904]
- Program of Shanghai Subject Chief Scientist [10XD1404500]
- Shanghai Science and Technology Commission [08411965000]
- Ph.D. Programs Foundation of Ministry of Education of China
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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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