Role of cancer stem cells and epithelial-mesenchymal transition in the invasion and metastasis in oral squamous cell carcinoma

• Project/Area Number: 25462940
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pathobiological dentistry/Dental radiology
• Research Institution: Aichi Gakuin University
• Principal Investigator: Goto Mitsuo 愛知学院大学, 歯学部, 講師 (60645191)
• Co-Investigator(Kenkyū-buntansha): 中西 速夫 愛知県がんセンター(研究所), その他部局等, その他(移行) (20207830)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 口腔扁平上皮がん / 低分化がん / CSC/EMT / podoplanin / TGF-β / PI3K/Akt経路 / 分子標的薬 / EMT/CSC / シグナル伝達 / Wnt/beta-catenin経路

Outline of Final Research Achievements

Cancer stem cells (CSC) and epithelial-mesenchymal transition (EMT) are reportedly involved in tumor invasion and metastasis in oral squamous cell carcinoma (OSCC). However, molecular base of this relationship remains unclear. Here, we focused on podoplanin (PDPN) to investigate its role in cancer stemness and EMT of OSCC. We developed a panel of UMSCC81B cell lines including parent cells, CSC subline, and EMT subline.
PDPN expression of parent and CSC cells was significantly higher than EMT cell. In vitro analysis revealed that PDPN expression of parent and CSC cells was down-regulated by HDAC inhibitors, whereas expressions of differentiation markers were up-regulated by the HDAC treatment. Knockdown of PDPN induced differentiation and suppressed cell growth. TGF-β induced PDPN expression. These results suggest that PDPN plays some important role in maintaining cancer stemness but not maintenance of EMT phenotype. PDPN would be a new therapeutic target for cancer stem cell of OSCC.

Research Products

• [Presentation] 口腔扁平上皮癌におけるPodoplanin発現とがん幹細胞形質との関連に関する実験的検討 (2017)
  • Author(s): 後藤満雄、宮地 斉、落合栄樹、齋藤輝海、渡邉 哲、宮部 悟、欄 真一郎、中西速夫、下郷和雄
  • Organizer: 第35回日本口腔腫瘍学会総会・学術大会
  • Place of Presentation: 福岡県 福岡市
  • Year and Date: 2017-01-26
• [Presentation] Role of podoplanin expression and its potential as a targeting molecule for oral squamous cell carcinomas (2015)
  • Author(s): Mitsuo Goto, Hiroyuki Makihara, Mitsuhiko Ohta, Shinichiro Maseki, Yasuhisa Hasegawa, Kenji Yoshida, Hayao Nakanishi, Kenichi Kurita
  • Organizer: 22nd International Conference on Oral and Maxillofacial Surgery
  • Place of Presentation: Melbourne, Australia
  • Year and Date: 2015-10-27
  • Int'l Joint Research
• [Presentation] Biological significance and regulation of podoplanin expression in oral squamous cell carcinomas. (2014)
  • Author(s): Mitsuo Goto, Hiroyuki Makihara, Mitsuhiko Ohta, Shinichiro Maseki, Yasuhisa Hasegawa, Hayao Nakanishi, Kenichi Kurita
  • Organizer: American Association of Oral and Maxillofacial Surgeons, 96th Annual Meeting, Scientific Sessions & Exhibition
  • Place of Presentation: Honolulu, Hawaii, USA
  • Year and Date: 2014-09-08 – 2014-09-13