CD98hc as a marker of radiotherapy-resistant cancer stem cells in head and neck squamous cell carcinoma

INTRODUCTION: The prognosis of head and neck squamous cell carcinoma (HNSCC) is generally good in cases of high radiation sensitivity but poor in cases exhibiting radiation resistance; this resistance has been attributed to the presence of cancer stem cells. In recent years, CD98hc overexpression has been associated with poor prognosis in various types of cancers. CD98 is a heterodimer of heavy and light chains and is strongly involved in cell proliferation, survival, migration, and adhesion. We investigated whether CD98hc can be used as a cancer stem cell marker for HNSCC. MATERIAL AND METHODS: We exposed five HNSCC cell lines to a total radiation dose of 60 Gy administered in 2 Gy fractions on consecutive days to investigate changes in CD98hc expression. Furthermore, we separated CD98-positive and CD98-negative cell populations to comparatively investigate the properties of each. RESULTS: Radiation resistance was observed in all five cell lines, and resistant cells exhibited CD98hc overexpression, with enhanced spheroid formation, migratory, and invasive abilities. Radiation-resistant cell lines were separated into CD98-positive and CD98-negative populations. CD98hc-positive radiation-resistant cell lines exhibited enhanced spheroid formation, invasion, and plating efficiency as well as strong tumorigenicity in nude mice. CONCLUSIONS: CD98hc-positive cells exhibited cancer stem cell-like properties in all cell lines. Thus, CD98hc is a potential marker of radiation sensitivity as well as a potential therapeutic target for improved survival rates of patients with HNSCC.