J Cancer 2017; 8(12):2384-2393. doi:10.7150/jca.19486

Research Paper

Interferon-α Promotes the Expression of Cancer Stem Cell Markers in Oral Squamous Cell Carcinoma

Hailong Ma1#, Shufang Jin1,2#, Wenyi Yang1, Zhuowei Tian1, Shuli Liu1, Yang Wang1, Ge Zhou3, Mei Zhao3, Shalva Gvetadze4, Zhiyuan Zhang1,✉, Jingzhou Hu1,✉

1. Department of Oral Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai 200011, China
2. Department of Oral and Maxillofacial Surgery, The Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou 310009, China
3. Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA
4. Central Research Institute of Dentistry and Maxillofacial Surgery, Congenital Maxillofacial Defects and Deformations, Timura Frunze 16, Moscow 119034, Russia
#Hailong Ma and Shufang Jin contributed equally to this study.

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Ma H, Jin S, Yang W, Tian Z, Liu S, Wang Y, Zhou G, Zhao M, Gvetadze S, Zhang Z, Hu J. Interferon-α Promotes the Expression of Cancer Stem Cell Markers in Oral Squamous Cell Carcinoma. J Cancer 2017; 8(12):2384-2393. doi:10.7150/jca.19486. Available from http://www.jcancer.org/v08p2384.htm

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Objectives: IFNα can stimulate an antitumor immune response and has a direct inhibition on cancer cells. This study is to test whether IFNα can activate dormant cancer stem cell (CSC) in oral squamous cell carcinoma (OSCC) to facilitate their elimination by chemotherapy.

Materials and methods: Nude mouse transplantation tumor model was established and administrated with IFNα and saline. The influence on CD44 and ALDH1A1 expression under IFNα treatment was detected by in vivo experiments. Flow cytometry, western blot, and immunofluorescence were used to detect the expression of CD44 and ALDH1A1 after INFa treatment in OSCC cell lines. Tumorsphere formation assay was conducted under incubation with IFNα for 2 weeks. Chromatin immunoprecipitation (ChIP) assays was used to examine the IFNα-induced transcriptional regulation of CD44 and ALDH1A1 expression. That IFNα-primed enhanced killing effect of chemotherapy was evaluated by MTT and western blot.

Results: IFNα transcriptionally activated the expression of CD44 and ALDH1A1 expression both in vivo and in vitro. IFNα-primed enhanced the cytotoxic inhibition effect of CDDP, erlotinib and nimotuzumab on OSCC cells.

Conclusion: These results suggest that IFNα could be administrated to patients prior to chemotherapeutic drugs, which will facilitate the killing of cancer stem cells in OSCC.

Keywords: Interferon alpha, CD44, ALDH1A1, Oral squamous cell carcinoma