CD98hc as a marker of radiotherapy-resistant cancer stem cells in head and neck squamous cell carcinoma
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Department of Otorhinolaryngology and Head-and-Neck Surgery, Akita University Graduate School of Medicine, Akita, Japan
Department of Molecular and Tumour Pathology, Akita University Graduate School of Medicine, Akita, Japan
Submission date: 2019-06-27
Final revision date: 2019-10-28
Acceptance date: 2019-11-19
Online publication date: 2020-02-11
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.

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.

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.