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 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.