Resistance to apoptosis-inducing stimuli in CD44+ head and neck squamous cell carcinoma cells

Head Neck. 2012 Mar;34(3):336-43. doi: 10.1002/hed.21732. Epub 2011 Apr 5.

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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / physiology*
  • Apoptosis Regulatory Proteins / physiology*
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology*
  • Carcinoma, Squamous Cell / physiopathology
  • Cell Culture Techniques
  • Cell Cycle / physiology
  • Cell Line, Tumor
  • Cell Proliferation
  • Head and Neck Neoplasms / metabolism
  • Head and Neck Neoplasms / pathology*
  • Head and Neck Neoplasms / physiopathology
  • Humans
  • Hyaluronan Receptors / physiology*
  • Neoplasm Proteins / metabolism
  • Neoplastic Stem Cells
  • Squamous Cell Carcinoma of Head and Neck
  • Tumor Necrosis Factors / metabolism

Substances

  • Apoptosis Regulatory Proteins
  • Hyaluronan Receptors
  • Neoplasm Proteins
  • Tumor Necrosis Factors