Nicotine Induces Lymph Node Metastasis of Oral Cancer Cells through EGFR Activation

• Project/Area Number: 26463004
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Okayama University
• Principal Investigator: IBARAGI Soichiro 岡山大学, 医歯薬学総合研究科, 助教 (80549866)
• Co-Investigator(Kenkyū-buntansha): 佐々木 朗 岡山大学, 医歯薬学総合研究科, 教授 (00170663)
• Research Collaborator: Hassan Mohammad Monsur Charles Sturt University, School of Dentistry & Health Sciences ; Hu Guo-Fu Molecular Oncology Research Institute, Tufts Medical Center
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: ニコチン / EGFR / リンパ管新生 / 口腔癌

Outline of Final Research Achievements

Nicotine, which is one of the main component of tobacco, is absorbed from oral mucosa and pulmonary alveoli by smoking, and moves to blood. Nicotine in blood binds to nicotinic acetylcholine receptor (nAChR) in central nervous system and relates to tobacco addiction. Recently, it has been reported that nicotine promotes proliferation and invasion in breast cancer cells through epidermal growth factor receptor (EGFR) activation. However, the role of nicotine in oral cancer cells is still unknown although oral cavity is most exposed organ to tobacco smoke. Therefore, this study assessed the effects of nicotine on oral cancer cells. Nicotine increased lymph node metastasis of oral cancer cells in animal model.The mechanism underlying the tumor progressive effects of nicotine in oral cancer cells consists of upregulation of cell proliferation, migration and invasion via the activation of EGFR.

Research Products

• [Int'l Joint Research] Tufts Medical Center(米国)
• [Int'l Joint Research] Charles Sturt University(オーストラリア)
• [Int'l Joint Research] Tufts Medical Center/Molecular Oncology Research Institute(米国)
• [Journal Article] Expression and Roles of CCN2 in Dental Epithelial Cells (2015)
  • Author(s): Shimo T, Koyama E, Kurio N, Matsumoto K, Okui T, Ibaragi S, Yoshioka N, Sasaki A.
  • Journal Title: In Vivo Volume: 29 Pages: 189-195
  • Peer Reviewed
• [Journal Article] Synthetic (+)-terrein suppresses interleukin-6/soluble interleukin-6 receptor induced-secretion of vascular endothelial growth factor in human gingival fibroblasts. (2014)
  • Author(s): Mandai H, Omori K, Yamamoto D, Tsumura T, Murota K, Yamamoto S, Mitsudo K, Ibaragi S, Sasaki A, Maeda H, Takashiba S, Suga S.
  • Journal Title: Bioorganic & Medicinal Chemistry Volume: 22 Pages: 5338-44
• [Journal Article] Neamine Inhibits Oral Cancer Progression by Suppressing Angiogenin-mediated Angiogenesis and Cancer Cell Proliferation」 (2014)
  • Author(s): Kishimoto K Yoshida S, Ibaragi S, Yoshioka N, Hu GF, Sasaki A.
  • Journal Title: Anticancer Research Volume: 34 Pages: 2113-21
• [Presentation] Nicotine Induces Lymph Node Metastasis of Oral Cancer Cells through EGFR Activation (2017)
  • Author(s): Soichiro Ibaragi; Shinichi Kodama; Daisuke Kuwajima; Tatsuo Okui; Norie Yoshioka; Tsuyoshi Shimo; Akira Sasaki
  • Organizer: 6th World Oral Cancer Congress of the International Academy of Oral Oncology (IAOO)
  • Place of Presentation: インド
  • Year and Date: 2017-05-17
  • Int'l Joint Research
• [Presentation] 口腔癌細胞におけるニコチンと上皮成長因子受容体の関連性について (2016)
  • Author(s): 桑島大介，伊原木聰一郎，高畠清文，吉岡徳枝，岸本晃治，志茂 剛，長塚 仁，佐々木 朗
  • Organizer: 第７０回NPO法人日本口腔科学会学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2016-04-16
• [Presentation] 口腔癌細胞におけるニコチンと上皮成長因子受容体の関連性について (2016)
  • Author(s): 桑島大介，伊原木聰一郎，高畠清文，吉岡徳枝，岸本晃治，志茂 剛，長塚 仁，佐々木 朗
  • Organizer: 第70回 NPO法人日本口腔科学会学術集会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2016-04-16