title: Head neck squamous cell carcinoma c-Met⁺ cells display cancer stem cell properties and are responsible for cisplatin-resistance and metastasis.
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.
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Stomatology, Tongji University, Shanghai, China.
authors.forename: Shuyang
authors.initials: S
authors.lastname: Sun
authors.forename: Zuolin
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology*; D002455:Cell Division; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000473:pathology*; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D019859:Proto-Oncogene Proteins c-met; D002945:Cisplatin