The prognosis in patients with advanced
head and neck squamous cell carcinoma (
HNSCC) is widely affected by the resistance to
chemotherapy. As a culture scaffold,
collagen I was showed to promote CSC (cancer stem cell) properties of
cancer cells which could be used as in vitro models to study the chemoresistance in
HNSCC. Endoplasmic reticulum (ER) stress is a cellular stress condition which could affect
tumor progression and promote the anti-
tumor effects of certain drugs. However, the impact of ER stress on
collagen I induced CSC properties and chemoresistance of
HNSCC cells has not been addressed. In this study we investigated the effects of
tunicamycin (TM) induced ER stress on the stemness and sensitivity to chemotherapeutic drugs of FaDu hypopharyngeal
carcinoma cells in 3D (three-dimensional)
collagen I cultures and mouse xenograft models. Our study revealed that
Collagen I scaffold promoted CSC properties and increased G1 population of FaDu cells in 3D cultures, accompanied by maturation of
integrin β1 and enhanced activated TGF-β1 concentration. Compared to 2D (two-dimensional) cultured cells, cells in 3D
Collagen I scaffold exhibited significantly increased resistance to chemotherapeutic drugs of
cisplatin and
paclitaxel. Further analysis revealed that TM induced ER stress preferentially attenuated chemoresistance of FaDu cells in 3D
collagen I, downregulated their CSC properties and TGF-β1 concentration and resulted in deglycosylation of
integrin β1. TM was further evaluated in the mouse xenograft models and showed significant
tumor growth inhibition in combination with
paclitaxel than either TM or
paclitaxel alone. Taken together, Our findings suggest that TM-induced ER stress potentiates anticancer efficacy of FaDu cells in 3D cultures and in vivo, and highlight implications for targeting
chemotherapy-resistant cancer stem cells under ER stress conditions.