title: CD44 and SSEA-4 positive cells in an oral cancer cell line HSC-4 possess cancer stem-like cell characteristics.
abstract: BACKGROUND
  Cancer may be derived from cancer stem-like cells (CSCs), which are tumor-initiating cells that have properties similar to those of stem cells. Identification and isolation of CSCs needs to be improved further.
  
  
  METHODS
  CSCs markers were examined in human oral cancer cell lines by flow cytometry. The stem cell properties of subpopulations expressing different markers were assessed further by in vitro sphere formation assays, expression of stemness genes, drug resistance assays, and the ability to form tumors in nude mice.
  
  
  RESULTS
  We demonstrated that CSCs could be isolated by the cell surface markers CD44 and stage-specific embryonic antigen-4 (SSEA-4). CD44+SSEA-4+ cells exhibited cancer stem-like properties, including extensive self-renewal into the bulk of cancer cells. In vivo xenograft experiments indicated that CD44+SSEA-4+ cells exhibit the highest tumorigenic capacity compared with the remaining subpopulations and parental cells. Double-positive cells for CD44 and SSEA-4 exhibited preferential expression of some stemness genes and were more resistant to the anticancer drugs, cisplatin and 5-fluorouracil (5-FU). In addition, cells expressing CD44 and SSEA-4 were detected in all tumor specimens analyzed, while coexpression of CD44 and SSEA-4 was not detectable in normal oral mucosa.
  
  
  CONCLUSIONS
  Our findings suggest that CD44+SSEA-4+ cells exhibit the characteristics of CSCs in oral squamous cell carcinoma and provide a target for the development of more effective therapies.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Japan.
authors.forename: Zenko
authors.initials: Z
authors.lastname: Noto
authors.forename: Toshiko
authors.initials: T
authors.lastname: Yoshida
authors.forename: Motonori
authors.initials: M
authors.lastname: Okabe
authors.forename: Chika
authors.initials: C
authors.lastname: Koike
authors.forename: Moustafa
authors.initials: M
authors.lastname: Fathy
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Tsuno
authors.forename: Kei
authors.initials: K
authors.lastname: Tomihara
authors.forename: Naoya
authors.initials: N
authors.lastname: Arai
authors.forename: Makoto
authors.initials: M
authors.lastname: Noguchi
authors.forename: Toshio
authors.initials: T
authors.lastname: Nikaido
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000473:pathology*; D045744:Cell Line, Tumor; D064593:Heterografts; D006801:Humans; D018960:Hyaluronan Receptors / Q000032:analysis*; D051379:Mice; D009062:Mouth Neoplasms / Q000276:immunology / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000473:pathology*; D055746:Stage-Specific Embryonic Antigens / Q000032:analysis*
chemical_list: D014408:Biomarkers, Tumor; D018960:Hyaluronan Receptors; D055746:Stage-Specific Embryonic Antigens; C066584:stage-specific embryonic antigen-4
keywords: CD44; Cancer stem-like cells; Oral cancer cell line; SSEA-4