Analysis of mechanical stress-mediated control mechanism of cancer stem cell character in oral squamous cell carcinoma.

• Project/Area Number: 17K11837
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Hiroshima University
• Principal Investigator: Shigeishi Hideo 広島大学, 医系科学研究科(歯), 講師 (90397943)
• Co-Investigator(Kenkyū-buntansha): 太田 耕司 広島大学, 医系科学研究科(歯), 教授 (20335681) ; 小野 重弘 広島大学, 医系科学研究科(歯), 助教 (70379882)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 癌幹細胞 / 口腔癌 / ハイドロゲル / 細胞外基質 / ラミニン332 / 口腔扁平上皮癌

Outline of Final Research Achievements

We investigated changes in phenotype in CD44 high-oral squamous cell carcinoma cells that were cultured on laminin332-coated hydrogel with various degrees of stiffness. Mesenchymal-like morphology was observed when cells were cultured on 4.0 kPa laminin-coated hydrogel; amoeboid-like morphology was observed when cells were cultured on 1.0 kPa laminin-coated hydrogel. These results indicated that CD44high cells underwent mesenchymal to amoeboid transition when cultured on laminin-coated softer hydrogel.

Academic Significance and Societal Importance of the Research Achievements

CD44high口腔扁平上皮癌細胞は、ラミニン332にてコーテイングしたハイドロゲル上にて培養した結果、足場の弾性率の変化によりamoeboid様形態を示す細胞に変化することが明らかとなった。さらに、アクチン細胞骨格を制御するcofilin-1がamoeboid様細胞の形態維持に必要であることが示唆された。このことから、口腔癌幹細胞は周囲の細胞外基質や足場の弾性率に応じて、細胞形態や遺伝子発現パターンを柔軟に変化させることが可能であり、表現型および遺伝子発現の可塑性が口腔癌幹細胞の重要な特徴のひとつであることが明らかとなった。

Research Products

• [Journal Article] Effect of hydrogel stiffness on morphology and gene expression pattern of CD44high oral squamous cell carcinoma cells. (2019)
  • Author(s): Shigeishi H, Yokoyama S, Murodumi H, Sakuma M, Kato H, Higashikawa K, Takechi M, Ohta K, Sugiyama M.
  • Journal Title: Int J Clin Exp Pathol Volume: 18 Pages: 2826-2836
  • Peer Reviewed
• [Journal Article] Detection of oral bacteria on the tongue dorsum using PCR amplification of 16S ribosomal RNA and its association with systemic disease in middle-aged and elderly patients. (2019)
  • Author(s): Su CY, Shigeishi H, Nishimura R, Ohta K, Sugiyama M.
  • Journal Title: Biomed Rep Volume: 10 Pages: 70-76
  • Peer Reviewed
• [Journal Article] High HPV16 E6 viral load in the oral cavity is associated with an increased number of bacteria: A preliminary study. (2018)
  • Author(s): Shigeishi H, Sugiyama M, Ohta K, Yokoyama S, Sakuma M, Murozumi H, Kato H, Takechi M.
  • Journal Title: Biomed Rep Volume: 8 Pages: 59-64
  • Peer Reviewed
• [Journal Article] CD44high/ESAlow squamous cell carcinoma cell-derived prostaglandin E2 confers resistance to 5-fluorouracil-induced apoptosis in CD44high/ESAhigh cells (2018)
  • Author(s): Shigeishi H, Hashikata M, Yokoyama S, Sakuma M, Murozumi H, Kato H, Rahman MZ, Seino S, Ishioka Y, Ohta K, Takechi M, Sugiyama M
  • Journal Title: Int J Clin Exp Pathol Volume: 11 Pages: 2356-2363
  • Peer Reviewed
• [Journal Article] Human papillomavirus type 16 (HPV16) DNA copy number in oral rinse samples from oral cavity cancer patients. (2018)
  • Author(s): Shigeishi H, Yokoyama S, Ohta K, Takechi M, Sugiyama M.
  • Journal Title: Translational Research in Oral Oncology Volume: 3 Pages: 1-5
  • Peer Reviewed
• [Journal Article] Candida albicans β-Glucan-Containing Particles Increase HO-1 Expression in Oral Keratinocytes via a Reactive Oxygen Species/p38 Mitogen-Activated Protein Kinase/Nrf2 Pathway. (2018)
  • Author(s): Ishida Y, Ohta K, Naruse T, Kato H, Fukui A, Shigeishi H, Nishi H, Tobiume K, Takechi M.
  • Journal Title: Infect Immun Volume: 86
  • Peer Reviewed
• [Journal Article] Human Papillomavirus (HPV) 感染と口腔癌の関係について―最近の研究から―（総説） (2017)
  • Author(s): 重石英生，杉山 勝
  • Journal Title: 口腔衛生学会雑誌 Volume: 67 Pages: 149-159
  • Peer Reviewed
• [Journal Article] Differential regulation by IFN γ on TNF α induced chemokine expression in synovial fibroblasts from temporomandibular joint. (2017)
  • Author(s): Ohta K, Naruse T, Kato H, Ishida Y, Nakagawa T, Ono S, Shigeishi H, Takechi M.
  • Journal Title: Mol Med Rep Volume: 16 Pages: 6850-6857
  • Peer Reviewed
• [Journal Article] TNF-α-induced IL-6 and MMP-9 expression in immortalized ameloblastoma cell line established by hTERT. (2017)
  • Author(s): Ohta K, Naruse T, Ishida Y, Shigeishi H, Nakagawa T, Fukui A, Nishi H, Sasaki K, Ogawa I, Takechi M.
  • Journal Title: Oral Dis Volume: 23 Pages: 199-209
  • Peer Reviewed
• [Presentation] The effect of hydrogel stiffness on morphology and gene expression pattern in CD44high oral squamous cell carcinoma cells (2019)
  • Author(s): Sho Yokoyama, Hideo Shigeishi, Hiroshi Murozumi, Miyuki Sakuma, Hiroki Kato, Kouji Ohta, Masaru Sugiyama, Masaaki Takechi
  • Organizer: 第52回広島大学歯学会総会
• [Presentation] Human Papillomavirus (HPV)と口腔癌の関係について－最近の研究から－ 指定ワークショップ. 口腔癌検診とがん予防対策―口腔癌の罹患率・死亡率低減のための方策― (2018)
  • Author(s): 重石 英生
  • Organizer: 第63回日本口腔外科学会総会・学術大会
  • Invited
• [Presentation] 口腔のHPV感染とその危険因子の検索 (2017)
  • Author(s): 重石 英生，杉山 勝
  • Organizer: 第66回日本口腔衛生学会・総会
• [Presentation] 口腔のHPV感染の危険因子およびHPV陽性口腔癌の臨床病理学的特徴－最近の研究から－ (2017)
  • Author(s): 重石 英生，杉山 勝. 太田 耕司，東川 晃一郎，武知 正晃
  • Organizer: 第62 回日本口腔外科学会総会・学術大会