Analysis of the invasive mechanism of non-small lung cancer via cytokeratin collapse and development of anti-invasion therapy

• Project/Area Number: 25461190
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Kagawa University
• Principal Investigator: Bandoh Shuji 香川大学, 医学部, 講師 (60314928)
• Co-Investigator(Kenkyū-buntansha): ISII Tomoya 香川大学, 医学部附属病院, 助教 (80467836) ; KANAJI Nobuhiro 香川大学, 医学部附属病院, 助教 (60403789) ; HABA Reiji 香川大学, 医学部附属病院, 准教授 (90304584) ; FUJITA Jiro 琉球大学, 医学(系)研究科(研究院), 教授 (80209056)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: ビメンチン / 肺癌 / 浸潤能 / マトリゲル / 非小細胞肺癌 / サイトケラチン / 浸潤

Outline of Final Research Achievements

We evaluated the association between vimentin expression in resected non-small cell lung cancer(NSCLC) specimens and prognosis. Short-interfering RNA interference targeting vimentin and establishment of an invasive cell line by repeated selection of invasive cells using a Matrigel membrane invasion chamber system (MICS) were performed. A MICS was used to reveal the relationship between invasiveness and vimentin. Vimentin positivity was significantly associated with a poor prognosis and was significantly lower in squamous cell carcinoma than in adenocarcinoma. In in vitro experiments, silencing of vimentin reduced invasiveness. Highly invasive cell lines showed higher expression of vimentin than did the parental cells and decreased the invasive ability was reduced by knockdown of vimentin. Vimentin expression is associated with the prognosis via alteration of the invasive ability of NSCLC cells.

Research Products

• [Journal Article] Higher susceptibility of NOD/LtSz-scid II2rg (-/-) NSG mice to xenotransplanted lung cancer cell lines (2014)
  • Author(s): Kanaji N, Tadokoro A, Susaki K, Yokokura S, Ohmichi K, Haba R, Watanabe N, Bandoh S, Ishii T, Dobashi H, Matsunaga T
  • Journal Title: Cancer Manag Res Volume: 21 Pages: 431-436
  • DOI: 10.2147/cmar.s71185
  • Peer Reviewed / Open Access
• [Journal Article] EGFR mutation identifies distant squamous cell carcinoma as metastasis from lung adenocarcinoma (2013)
  • Author(s): Kanaji N, Bandoh S, Hayashi T, Haba R, Watanabe N, Ishii T, Kunitomo A, Takahama T, Tadokoro A, Imataki O, Dobashi H, Matsunaga T
  • Journal Title: World J Respirol Volume: 3 Pages: 38-43
  • Peer Reviewed
• [Presentation] Vimentinは非小細胞肺癌の浸潤能を亢進させ予後を悪化させる (2015)
  • Author(s): 田所 明、金地伸拓、井上卓哉、渡邊直樹、石井知也、坂東修二
  • Organizer: 第55回日本呼吸器学会学術講演会
  • Place of Presentation: 東京国際フォーラム
  • Year and Date: 2015-04-17
• [Presentation] iPat法により検出されたEGFRおよびALK遺伝子異常における治療効果の検討 (2013)
  • Author(s): 石井知也、高濱隆幸、田所 明、渡邊直樹、金地伸拓、坂東修二、松永卓也
  • Organizer: 第53回日本呼吸器学会学術講演会
  • Place of Presentation: 東京国際フォーラム