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CD 44 high / ALDH 1 high head and neck squamous cell carcinoma cells exhibit mesenchymal characteristics and GSK 3β‐dependent cancer stem cell properties
Author(s) -
Seino Sayaka,
Shigeishi Hideo,
Hashikata Miho,
Higashikawa Koichiro,
Tobiume Kei,
Uetsuki Ryo,
Ishida Yoko,
Sasaki Kazuki,
Naruse Takako,
Rahman Mohammad Zeshaan,
Ono Shigehiro,
Simasue Hiroshi,
Ohta Kouji,
Sugiyama Masaru,
Takechi Masaaki
Publication year - 2016
Publication title -
journal of oral pathology and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.887
H-Index - 83
eISSN - 1600-0714
pISSN - 0904-2512
DOI - 10.1111/jop.12348
Subject(s) - cd44 , cancer stem cell , sox2 , stem cell , stem cell marker , head and neck squamous cell carcinoma , homeobox protein nanog , cancer research , biology , mesenchymal stem cell , population , microbiology and biotechnology , chemistry , cell , cancer , induced pluripotent stem cell , biochemistry , medicine , embryonic stem cell , genetics , head and neck cancer , gene , environmental health
Background CD 44 and aldehyde dehydrogenase 1 ( ALDH 1) have been shown to be useful markers for identification of cancer stem cells ( CSC s). We previously reported that glycogen synthase kinase 3β ( GSK 3β) is involved in regulation of the self‐renewal ability of head and neck squamous cell carcinoma ( HNSCC ) CSC s. The purpose of the present study was to clarify the role of GSK 3β in CD 44 high / ALDH 1 high HNSCC cells. Methods Cells with greater expression of CD 44 and higher ALDH 1 enzymatic activity were FACS sorted from the OM ‐1 HNSCC cell line. The self‐renewal ability of CD 44 high / ALDH 1 high cells was then examined using a tumor sphere formation assay. mRNA expressions of the stem cell markers Sox2, Oct4, and Nanog, as well as GSK 3β were evaluated by real‐time RT ‐ PCR . Results CD 44 high / ALDH 1 high cells exhibited higher tumor sphere forming ability and increased expression of stem cell markers as compared with CD 44 high / ALDH 1 low cells. Interestingly, spindle‐shaped cells positive for vimentin were found in the CD 44 high / ALDH1 high but not the CD 44 high / ALDH 1 low cell population. In addition, the ALDH 1 activity and sphere forming ability of CD 44 high / ALDH 1 high cells was significantly inhibited by GSK 3β knockdown. On the other hand, CD 44 high / ALDH1 low cells exhibited high epidermal growth factor receptor ( EGFR ) expression and increased cell growth. Conclusions Our results show that GSK 3β plays a major role in maintenance of stemness of CD 44 high / ALDH 1 high HNSCC cells. Additionally, they indicate a close relationship between CSC and mesenchymal characteristics in HNSCC .