Significance of hypoxia-responsive cancer stem cell markers in invasion and metastasis of oral cancer

• Project/Area Number: 16K11727
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Kagoshima University
• Principal Investigator: Hijioka Hiroshi 鹿児島大学, 医歯学域附属病院, 講師 (70305150)
• Co-Investigator(Kenkyū-buntansha): 石田 喬之 鹿児島大学, 医歯学域附属病院, 助教 (20404501) ; 久米 健一 鹿児島大学, 医歯学域歯学系, 助教 (60650067) ; 濱田 大治 鹿児島大学, 医歯学域医学系, 助教 (30771480) ; 谷本 昭英 鹿児島大学, 医歯学域医学系, 教授 (10217151) ; 中村 典史 鹿児島大学, 医歯学域歯学系, 教授 (60217875)
• Research Collaborator: Sugiura Tsuyoshi
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2016: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 口腔癌 / がん幹細胞 / 上皮間葉移行 / EMT / 低酸素 / 癌幹細胞 / 浸潤転移

Outline of Final Research Achievements

Cervical lymph node metastasis is the greatest prognostic factor in the treatment of oral cancer, and its control is essential for improving treatment outcome. For that purpose, it is necessary to elucidate the mechanism of metastasis. Recently, it has been suggested that epithelial-mesenchymal transition (EMT) is an important step in the process of metastasis, and the association between EMT and cancer stem cells (CSC) has been noted.
In this study, we found that BRACHYURY and SOX2 synergistically promote cancer stemness in oral cancer cells. This finding points to the importance of gene or protein networks associated with BRACHYURY and SOX2 in the development and maintenance of the CSC phenotype.

Academic Significance and Societal Importance of the Research Achievements

口腔癌の治療において頸部リンパ節転移は最大の予後因子であり、治療成績向上にはその制御が不可欠である。そのためには転移のメカニズムを解明する必要があるが、その詳細は未だ不明な点が多い。
本研究において転移に必須であるEMTおよびがん幹細胞性の獲得、維持にBRACHYURYおよびSOX2が重要な役割を果たすことが明らかになり、これらを制御することで浸潤・転移を防ぐ新たな治療方法の開発に繋がることが期待できる。

Research Products

• [Journal Article] Transfection of T-Box Transcription Factor BRACHYURY and SOX2 Synergistically Promote Self-Renewal and Invasive Phenotype in Oral Cancer Cells (2018)
  • Author(s): Akimoto Naonari、Nakamura Kodai、Hijioka Hiroshi、Kume Kenichi、Matsumura Yoshiaki、Sugiura Tsuyoshi
  • Journal Title: International Journal of Molecular Sciences Volume: 19 Issue: 11 Pages: 3620-3620
  • DOI: 10.3390/ijms19113620
  • Peer Reviewed / Open Access
• [Journal Article] A diagnosis system for detecting cervical lymph node metastasis in oral squamous cell carcinoma: Collective consideration of the results of multiple imaging modalities (2017)
  • Author(s): Takayuki Ishida, Hiroshi Hijioka, Kenichi Kume, Takuya Yoshimura, Akihiko Miyawaki, Etsuro Nozoe, Shigeaki Suenaga, Hiroko Indo, Hideyuki J. Majima, Norifumi Nakamura
  • Journal Title: Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology Volume: 29 Issue: 3 Pages: 210-216
  • DOI: 10.1016/j.ajoms.2016.12.007
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] PCP4/PEP19 promotes migration, invasion and adhesion in human breast cancer MCF-7 and T47D cells (2016)
  • Author(s): 4.Yoshimura T, Hamada T, Hijioka H, Souda M, Hatanaka K, Yoshioka T, Yamada S, Tsutsui M, Umekita Y, Nakamura N, Tanimoto A
  • Journal Title: Oncotarget Volume: 7 Issue: 31 Pages: 49065-49074
  • DOI: 10.18632/oncotarget.7529
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] 当科における過去3年間の口腔癌の治療成績に関する臨床病理学的検討 (2018)
  • Author(s): 山城 康太(鹿児島大学 大学院医歯学総合研究科顎顔面機能再建学講座顎顔面疾患制御学分野), 浜田 倫史, 内野 祥徳, 有村 麻弥, 中村 康大, 松村 吉晃, 後藤 雄一, 別府 真広, 比地岡 浩志, 杉浦 剛
  • Organizer: 日本口腔外科学会総会学術学会
• [Presentation] 口腔扁平上皮癌に対する術前S-1放射線同時併用療法の臨床的検討 (2017)
  • Author(s): 品川憲穂、比地岡浩志、石田喬之、久米健一、本庄希江、野村綾子、野添悦郎、中村典史
  • Organizer: 第21回九州地区口腔癌研究会