Elucidation of the mechanism by which extracellular vesicles miRNA induces abnormalities in tumor endothelial cells and development of novel cancer diagnostics and therapy

• Project/Area Number: 16H06603
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Surgical dentistry
• Research Institution: Hokkaido University
• Principal Investigator: Torii Chisaho 北海道大学, 遺伝子病制御研究所, 客員研究員 (00780561)
• Project Period (FY): 2016-08-26 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 腫瘍血管 / 細胞外小胞 / miRNA / 薬剤耐性 / 腫瘍

Outline of Final Research Achievements

In this study, we investigated whether extracellular vesicles (EVs) involved in drug resistance in tumor endothelial cells. EVs were isolated from low and high metastatic tumor. We identified miRNA-X which was contained higher level in high metastatic tumor EVs than in low metastatic tumor EVs. miR-X was transported by EVs into endothelial cells and downregulated target gene Y expression. It induced drug resistance to 5-FU in endothelial cells. In the future, we will investigate whether miRNA-X relates to pathological factors and prognosis using clinical samples in order to develop novel cancer diagnostics and therapy.

Research Products

• [Journal Article] Aneuploidy of murine immortalized endothelial cell line, MS1. (2017)
  • Author(s): Hida K., Maishi N., Dorcas Akuba-Muhyia Annan, Kondoh M., Hojo T., Umma Habiba, Ohga N., Ishikawa K, Sato M., Torii C., Yanagiya M., Morimoto M., Hida Y., Shindoh M.
  • Journal Title: J Oral Biosci Volume: 59 Issue: 1 Pages: 50-54
  • DOI: 10.1016/j.job.2016.10.004
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Vasohibin-1 as a novel prognostic factor for head and neck squamous cell carcinoma (2017)
  • Author(s): Torii C., Hida Y., Shindoh M., Akiyama K., Ohga N., Maishi N., Ohiro Y., Ono M., Totsuka Y., Kitagawa Y., Tei K., Sato Y., *Hida K.
  • Journal Title: Anticancer Res Volume: 37(3) Pages: 1219-1225
  • Peer Reviewed
• [Journal Article] Tumor Endothelial Cells with High Aldehyde Dehydrogenase Activity Show drug resistance (2017)
  • Author(s): 9.Hida K, Maishi N, Akiyama K, Ohmura-Kakutani H, Torii C, Ohga N, Osawa T, Kikuchi H, Morimoto H, Morimoto M et al
  • Journal Title: Cancer Sci Volume: 108 Issue: 11 Pages: 2195-2203
  • DOI: 10.1111/cas.13388
  • NAID: 120006373733
  • Peer Reviewed / Open Access
• [Journal Article] Vasohibin-1 as a novel prognostic factor for head and neck squamous cell carcinoma (2017)
  • Author(s): Torii C., Hida Y., Shindoh M., Akiyama K., Ohga N., Maishi N., Ohiro Y., Ono M., Totsuka Y., Kitagawa Y., Tei K., Sato Y., Hida K.
  • Journal Title: Anticancer Res Volume: 37 Issue: 3 Pages: 1219-1225
  • DOI: 10.21873/anticanres.11437
  • Peer Reviewed / Open Access
• [Journal Article] Aneuploidy of murine immortalized endothelial cell line, MS1 (2017)
  • Author(s): Hida K., Maishi N., Dorcas Akuba-Muhyia Annan, Kondoh M., Hojo T., Umma Habiba, Ohga N., Ishikawa K, Sato M., Torii C., Yanagiya M., Morimoto M., Hida Y., Shindoh M
  • Journal Title: J Oral Biosci Volume: 59 Pages: 50-54
  • Peer Reviewed
• [Journal Article] Tumor endothelial cells express high pentraxin 3 levels (2016)
  • Author(s): Hida K., Maishi N., Kawamoto T., Akiyama K., Ohga N., Hida Y., Yamada K., Hojo T., Kikuchi H., Sato M., Torii C., Shinohara N., Shindoh M
  • Journal Title: Pathol Int Volume: 66 Issue: 12 Pages: 687-694
  • DOI: 10.1111/pin.12474
  • Peer Reviewed / Open Access
• [Journal Article] Comparison of characteristics of mouse immortalized normal endothelial cells, MS1 and primary cultured endothelial cells (2016)
  • Author(s): Hida K., Maishi N., Torii C., Yanagiya M., Annan Akuba-Muhyia Dorcas., Morimoto M., Alam Mohammad Towfik
  • Journal Title: Hokkaido Journal of Dental Science Volume: 37 Pages: 40-48
  • NAID: 120005855959
  • Peer Reviewed
• [Journal Article] Tumor angiogenesis-characteristics of tumor endothelial cells. (2016)
  • Author(s): Hida K, Maishi N, Torii C, Hida Y.
  • Journal Title: Int J Clin Oncol Volume: 21 Issue: 2 Pages: 206-212
  • DOI: 10.1007/s10147-016-0957-1
  • Peer Reviewed
• [Presentation] 高転移性腫瘍miRによる血管内皮における薬剤耐性誘導 (2017)
  • Author(s): 間石奈湖, 鳥居ちさほ, 川本泰輔, 森本真弘, 秋山廣輔, 吉岡祐亮, Alam Mohammad Towfik, 南 敬, 落谷孝広, 樋田泰浩, 樋田京子
  • Organizer: 第26回日本がん転移学会学術集会
• [Presentation] Correlation between endothelial CXCR7 expression and clinic pathological factors in oral squamous cell carcinoma (OSCC) (2017)
  • Author(s): Randa Ibrahim Dawood, Yanagiya M., Maishi N., Hida Y., Torii C., Kikuchi H., Ohga N., Tei K., Kitakura T., Shindoh M., Hida K.
  • Organizer: 第5回がんと代謝研究会
• [Presentation] 高転移性腫瘍エクソソームmiRによる血管内皮の薬剤耐性誘導 (2017)
  • Author(s): 森本真弘，鳥居ちさほ，川本泰輔，間石奈湖，吉岡祐亮，落谷孝広，樋田泰浩，樋田京子
  • Organizer: 第5回がんと代謝研究会
• [Presentation] Tumor endothelial cells acquire drug resistance by exosomal-miR derived from high metastatic tumor (2016)
  • Author(s): Hida K., Torii C., Maishi N., Morimoto M., Akiyama K., Kawamoto T., Minami T., Yoshioka Y., Mohammad Towfik Alam, Shindoh M., Hida Y., Ochiya T
  • Organizer: The 19th International Vascular Biology Meeting
  • Place of Presentation: Boston (America)
  • Year and Date: 2016-11-02
• [Presentation] 高転移性腫瘍エクソソームmiRNAは血管内皮のIL6を誘導し血管新生阻害療法への耐性を誘導する (2016)
  • Author(s): 森本真弘, 鳥居ちさほ, 川本泰輔, 秋山廣輔, 間石奈湖, 吉岡祐亮, 落谷孝広, 柳谷美沙, 菊地 央, 北川善政, 鄭漢 忠, 進藤正信, 樋田泰浩, 樋田京子
  • Organizer: 第7回IGM研究交流会
  • Place of Presentation: 北海道大学（北海道札幌市）
  • Year and Date: 2016-10-18
• [Presentation] 高転移性腫瘍miRによる血管内皮におけるIL-6を介した薬剤耐性誘導 (2016)
  • Author(s): 間石奈湖，鳥居ちさほ，川本泰輔，秋山廣輔，吉岡祐亮，落谷孝広，柳谷美沙，森本真弘，菊地 央，鄭 漢忠，北川善政，進藤正信，樋田泰浩，樋田京子
  • Organizer: 第49回北海道病理談話会
  • Place of Presentation: 北海道大学 （北海道札幌市）
  • Year and Date: 2016-10-15
• [Presentation] 高転移性腫瘍miRによる血管内皮におけるIL-6を介した薬剤耐性誘導 (2016)
  • Author(s): 森本真弘，鳥居ちさほ，秋山廣輔，川本泰輔，間石奈湖，鄭漢忠，北川善政，進藤正信，樋田泰浩，樋田京子
  • Organizer: 第8回日本RNA-i研究会
  • Place of Presentation: グランドプリンスホテル広島（広島県広島市）
  • Year and Date: 2016-09-02
• [Remarks] 北海道大学 遺伝子病制御研究所 フロンティア研究ユニット 血管生物学研究室ホームページ
  • URL: http://www.igm.hokudai.ac.jp/vascular-biology/