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Head neck squamous cell carcinoma c‐Met + cells display cancer stem cell properties and are responsible for cisplatin‐resistance and metastasis
Author(s) -
Sun Shuyang,
Wang Zuolin
Publication year - 2011
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.25927
Subject(s) - head and neck squamous cell carcinoma , cd44 , cancer stem cell , cancer research , metastasis , population , stem cell , biology , cancer , cell , c met , side population , cisplatin , hepatocyte growth factor , cancer cell , pathology , head and neck cancer , medicine , receptor , microbiology and biotechnology , chemotherapy , genetics , environmental health
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.