Studies in experimental animals of oral cancer metastasis suppression using a nutritional immunity (EPA)

• Project/Area Number: 25463114
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Kumamoto University
• Principal Investigator: Ogi Hidenao 熊本大学, 大学院生命科学研究部(医), 助教 (10315426)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 口腔がん / 転移 / EPA / TNF-α / TNFR1 / 扁平上皮癌 / 栄養免疫 / 口腔扁平上皮がん / 舌癌 / NF-κB

Outline of Final Research Achievements

Cancer cells (GSAS/N5) increased invasive activity 7-fold in a TNF-α receptor TNFR1-dependent manner and enhanced TNF- α and TNFR1 mRNA expression. In the highly metastatic cells, NF-B activation was up-regulated via elevated phosphorylation of Akt and Ikk/ in the signaling pathway and secretion of TNF-α ,active MMP-2 and MMP-9 increased.; TNF- activates NF-κB and activated NF-κB induces further TNF- secretion, leading to increase of active MMP release and promotion of invasion and metastasis of the cells. GSAS/N5 cells that were injected into the nude mouse tongue and harvested from metastasized lungs multiplied angiopoietin-like 4 (angptl4) expression with enhanced migration activity, which indicated a possible involvement of angptl4 in lung metastasis of the cells. These results suggest that TNF-α and angptl4 promote metastasis of the oral cancer cells, thus these molecules may be therapeutic targets for patients with tongue cancer.

Research Products

• [Journal Article] Phase II clinical trial of multiple peptide vaccination for advanced head and neck cancer patients revealed induction of immune responses and improved OS (2015)
  • Author(s): Yoshitake, Y., Fukuma, D., Yuno, A., Hirayama, M., Nakayama, H., Tanaka. T., Nagata, M., Takamune, Y., Kawahara, K., Nakagawa, Y., Yoshida, R., Hirosue, A., Ogi, H., Hiraki, A. , Jono, H., Hamada, A., Yoshida, K., Nishimura, Y., Nakamura, Y., Shinohara, M.
  • Journal Title: Clinical Cancer Research Volume: 21 Issue: 2 Pages: 312-321
  • DOI: 10.1158/1078-0432.ccr-14-0202
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Highly metastatic oral squamous carcinoma with autocrine of TNF-α acquire high invasion ability (2015)
  • Author(s): 田中 拓也
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-10-08
• [Presentation] 高転移性口腔扁平上皮癌はTNF-αの高発現によって高浸潤能を獲得している (2015)
  • Author(s): 田中拓也 中山秀樹 永田将士 吉田遼司 川原健太 中川純泰 松岡祐一郎 尾木秀直 平木昭吉武義泰 篠原正徳
  • Organizer: 第33回日本口腔腫瘍学会総会・学術大会
  • Place of Presentation: 奈良県新公会堂
  • Year and Date: 2015-01-29 – 2015-01-30