| Autor: |
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 |
| Předmět: |
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| Zdroj: |
Journal of Oral Pathology & Medicine; Mar2016, Vol. 45 Issue 3, p180-188, 9p, 1 Diagram, 5 Graphs |
| Abstrakt: |
Background: CD44 and aldehyde dehydrogenase 1 (ALDH1) have been shown to be useful markers for identification of cancer stem cells (CSCs). We previously reported that glycogen synthase kinase 3β (GSK3β) is involved in regulation of the self-renewal ability of head and neck squamous cell carcinoma (HNSCC) CSCs. The purpose of the present study was to clarify the role of GSK3β in CD44(high) /ALDH1(high) HNSCC cells. Methods: Cells with greater expression of CD44 and higher ALDH1 enzymatic activity were FACS sorted from the OM-1 HNSCC cell line. The self-renewal ability of CD44(high) /ALDH1(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 GSK3β were evaluated by real-time RT-PCR. Results: CD44(high) /ALDH1(high) cells exhibited higher tumor sphere forming ability and increased expression of stem cell markers as compared with CD44(high) /ALDH1(low) cells. Interestingly, spindle-shaped cells positive for vimentin were found in the CD44(high) /ALDH1(high) but not the CD44(high) /ALDH1(low) cell population. In addition, the ALDH1 activity and sphere forming ability of CD44(high) /ALDH1(high) cells was significantly inhibited by GSK3β knockdown. On the other hand, CD44(high) /ALDH1(low) cells exhibited high epidermal growth factor receptor (EGFR) expression and increased cell growth. Conclusions: Our results show that GSK3β plays a major role in maintenance of stemness of CD44(high) /ALDH1(high) HNSCC cells. Additionally, they indicate a close relationship between CSC and mesenchymal characteristics in HNSCC. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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