Examination of metastasis suppression effect focusing on tumor microenvironment around cancer stem cells

• Project/Area Number: 16K20575
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Surgical dentistry
• Research Institution: Kobe University
• Principal Investigator: Takeda Daisuke 神戸大学, 医学部附属病院, 助教 (80755637)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 口腔癌 / 癌幹細胞 / 幹細胞性因子 / 低酸素 / 分化度 / 疾患特異的生存率 / リンパ管新生能因子 / 頸部リンパ節転移 / 癌 / 歯学

Outline of Final Research Achievements

We investigated the expression of induced pluripotent stem cell related genes in vitro and in clinical samples to identify their relationships with hypoxia and tumorigenesis. Oral squamous cell carcinoma cells were used to show that expression levels of Oct3/4, Sox2, and Nanog were significantly increased in hypoxic condition in vitro and in moderately- and poorly-differentiated samples. The 3-year disease-specific survival rates of patients with high Oct3/4, Sox2 and Klf4 expression levels were significantly decreased. The expression levels of Podoplanin and LYVE-1 were significantly associated with cervical lymph node metastasis.

Academic Significance and Societal Importance of the Research Achievements

近年、癌幹細胞理論が提唱され、癌幹細胞が治療抵抗性や再発に重要な役割を果たしていると考えられている。また、癌幹細胞がその幹細胞の性質を維持するためには、癌細胞周囲微小環境が必要とされ、上皮系腫瘍である扁平上皮癌が、間葉組織で新たに転移巣を形成できるのは、自己複製能をもつ癌幹細胞様の細胞が存在するからだと考えられている。口腔扁平上皮癌においても、幹細胞性因子の発現が低酸素、分化度・転移能などの腫瘍の悪性度や予後と関連する可能性が考えられた。

Research Products

• [Journal Article] Induced Pluripotent Stem Cell-related Genes Correlate With Poor Prognoses of Oral Squamous Cell Carcinoma. (2019)
  • Author(s): Muraki Y, Hasegawa T, Takeda D, Ueha T, Iwata E, Saito I, Amano R, Sakakibara A, Akashi M, Komori T.
  • Journal Title: ANTICANCER RESEARCH Volume: 39 Issue: 3 Pages: 1205-1216
  • DOI: 10.21873/anticanres.13231
  • Peer Reviewed
• [Journal Article] Lymphangiogenesis and Lymph Node Metastasis in Oral Squamous Cell Carcinoma. (2018)
  • Author(s): Arimoto S, Hasegawa T, Takeda D, Saito I, Amano R, Akashi M, Komori T.
  • Journal Title: ANTICANCER RESEARCH Volume: 38 Issue: 11 Pages: 6157-6162
  • DOI: 10.21873/anticanres.12968
  • Peer Reviewed
• [Journal Article] Induced Pluripotent-stem-cell Related Genes Contribute to De-differentiation in Oral Squamous Cell Carcinoma. (2017)
  • Author(s): Takeda D, Hasegawa T, Ueha T, Iwata E, Harada R, Sakakibara A, Kawamoto T, Minamikawa T, Sakai Y, Komori T.
  • Journal Title: Anticancer Res. Volume: 37 Issue: 3 Pages: 1075-1082
  • DOI: 10.21873/anticanres.11419
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] 口腔扁平上皮癌における人工多能性幹細胞関連因子の発現について (2019)
  • Author(s): 武田大介・長谷川巧実・江崎友美・榊原晶子・明石昌也・南川勉・古森孝英
  • Organizer: 第37回(一社)日本口腔腫瘍学会総会・学術大会
• [Presentation] 口腔扁平上皮癌におけるリンパ管新生とリンパ節転移 (2019)
  • Author(s): 有本智美・長谷川巧実・八谷奈苗・天野利香・齊藤泉・武田大介・明石昌也
  • Organizer: 第64回(公社)日本口腔外科学会総会・学術大会
• [Presentation] 口腔扁平上皮癌におけるiPS細胞関連因子の発現率と予後の関連性 (2018)
  • Author(s): 江崎友美・長谷川巧実・武田大介・筧 康正・明石昌也・南川 勉・古森孝英
  • Organizer: 第63回(公社)日本口腔外科学会総会・学術大会