Isolation of Cancer Stem Cell and Identification of Signalling Pathway Related with Invasion and Metastasis in HPV- Oropharyngeal Cancer

• Project/Area Number: 17K11401
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Otorhinolaryngology
• Research Institution: Wakayama Medical University
• Principal Investigator: Gunduz Mehmet 和歌山県立医科大学, 医学部, 准教授 (70333507)
• Co-Investigator(Kenkyū-buntansha): 玉川 俊次 和歌山県立医科大学, 医学部, 講師 (40543781) ; 戸川 彰久 和歌山県立医科大学, 医学部, 講師 (70305762) ; 保富 宗城 和歌山県立医科大学, 医学部, 教授 (90336892)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 頭頸部癌 / 中咽頭癌 / HPV関連癌 / 癌幹細胞 / HPV / 頭頚部癌 / 口腔咽頭科学

Outline of Final Research Achievements

Isolated CSCs from HPV-negative OPC cell line, through magnetic activated cell sorting using CSC specific marker ALDH1 antibody, were characterized by sphere formation capacity, immunofluorescence staining, and CSC marker expression. CSC response to cisplatin treatment was evaluated via XTT-assay. Spheres of CSC of HPV-negative UTSCC-60A cell line were highly dark holospheres. RNA expression of CSC markers OCT4, SOX2, KLF4 and BMI1 were significantly higher in CSC. CSCs were significantly resistant to cisplatin treatment at various dosages as compared to nonCSC. HIST1H1T, TNSF18 and lin28 genes were detected to be candidate genes according to microarray data. HIST1H1T and TNSF18 have effect on CSC markers but this influence was not able to prevent CSC sphere formation and proliferation. lin28 gene had suppressed CSC markers and prevented CSC to form spheres which addresses this gene to be one of the candidate genes.

Academic Significance and Societal Importance of the Research Achievements

頭頸部癌における癌幹細胞と化学・放射線治療耐性の関係が明らかにすればより効率的治療効果が得られる。

Research Products

• [Journal Article] Identification and chemoresistance of cancer stem cells in HPV-negative oropharyngeal cancer (2020)
  • Author(s): Gunduz M, Gunduz E, Tamagawa S, Enomoto K, Hotomi M
  • Journal Title: Oncol Letters Volume: 19 Pages: 965-971
  • DOI: 10.3892/ol.2019.11127
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] HPV陰性口腔咽頭癌における癌幹細胞の特徴(Characterization of Cancer Stem Cell in HPV-negative Oropharyngeal Cancer) (2019)
  • Author(s): グンデゥズ・エスラ, グンデゥズ・メーメット , 玉川 俊次, 榎本 圭佑, 保富 宗城
  • Journal Title: 頭頸部癌 Volume: 45 Pages: 129-129
• [Journal Article] Characterization of Cancer Stem Cell in HPV-negative Oropharyngeal Cance (2019)
  • Author(s): Mehmet Gunduz, Esra Gunduz, Shunji Tamagawa, Keisuke Enomoto, Muneki Hotomi
  • Journal Title: Head Neck Volume: 投稿中
  • Int'l Joint Research
• [Presentation] HPV陰性口腔咽頭癌における癌幹細胞の特徴(Characterization of Cancer Stem Cell in HPV-negative Oropharyngeal Cancer) (2019)
  • Author(s): グンデゥズ・エスラ
  • Organizer: 第43回日本頭頸部癌学会
• [Presentation] Characterization of Cancer Stem Cell in HPV-negative Oropharyngeal Cancer (2018)
  • Author(s): Esra Gunduz, Mehmet Gunduz, Shunji Tamagawa, Keisuke Enomoto, Muneki Hotomi
  • Organizer: 第43回日本頭頸部癌学会
• [Presentation] HPV―中咽頭癌における癌幹細胞の同定と特徴の証明 (2018)
  • Author(s): グンデゥズ メーメット、グンデゥズ エスラ、玉川俊次、保富宗城
  • Organizer: 第119回日本耳鼻咽喉科学会総会