title: Resistance to apoptosis-inducing stimuli in CD44+ head and neck squamous cell carcinoma cells.
abstract: BACKGROUND
  CD44 was identified previously as a surface marker in cancer stem cells (CSCs) of head and neck squamous cell carcinoma (HNSCC). Most cancer treatments have been linked to the activation of the apoptosis-signaling pathway; however, the resistance mechanisms to apoptosis in CSCs have not yet been fully elucidated.
  
  
  METHODS
  The sensitivity of CD44+ cells to diverse apoptosis-inducing stimuli was compared with that of CD44- cells. Furthermore, cell cycle changes and the expression of anti-apoptosis-related genes were examined using flow cytometry and real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR).
  
  
  RESULTS
  CD44+ cells were resistant to various apoptosis-inducing stimuli. Moreover, CD44+ cells showed a higher proportion of cells in G2/M phase of the cell cycle and upregulation of Bcl-2 and inhibitor of apoptosis (IAP) family genes compared with CD44- cells.
  
  
  CONCLUSIONS
  Treatment resistance in CSCs seems to be regulated by various mechanisms, and, therefore, additional treatment strategies to target CSCs are required in patients with HNSCC.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Yamanashi, Faculty of Medicine, Chuo, Yamanashi, 409-3898, Japan. chikamatsu@yamanashi.ac.jp
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chikamatsu
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ishii
authors.forename: Goro
authors.initials: G
authors.lastname: Takahashi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Okamoto
authors.forename: Motohiro
authors.initials: M
authors.lastname: Moriyama
authors.forename: Koichi
authors.initials: K
authors.lastname: Sakakura
authors.forename: Keisuke
authors.initials: K
authors.lastname: Masuyama
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000502:physiology*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D018929:Cell Culture Techniques; D002453:Cell Cycle / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D018960:Hyaluronan Receptors / Q000502:physiology*; D009363:Neoplasm Proteins / Q000378:metabolism; D014411:Neoplastic Stem Cells; D000077195:Squamous Cell Carcinoma of Head and Neck; D048069:Tumor Necrosis Factors / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D018960:Hyaluronan Receptors; D009363:Neoplasm Proteins; D048069:Tumor Necrosis Factors