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

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 antiapoptosis-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. (C) 2011 Wiley Periodicals, Inc. Head Neck 34: 336-343, 2012