Development of the drugs targeting lung tumor endothelial cells and the companion diagnosis

• Project/Area Number: 24390324
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Thoracic surgery
• Research Institution: Hokkaido University
• Principal Investigator: Hida Yasuhiro 北海道大学, 大学病院, 准教授 (30399919)
• Co-Investigator(Kenkyū-buntansha): KAGA KICHIZO 北海道大学, 北海道大学病院, 講師 (80224335) ; MATSUI YOSHIRO 北海道大学, 大学院医学研究科, 教授 (90219379) ; 加藤 達哉 北海道大学, 大学病院, 医員 (20624232) ; 樋田 京子 北海道大学, 歯学研究科(研究院), 特任准教授 (40399952)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥19,110,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥4,410,000); Fiscal Year 2014: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2013: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000); Fiscal Year 2012: ¥13,260,000 (Direct Cost: ¥10,200,000、Indirect Cost: ¥3,060,000)
• Keywords: 肺癌 / 血管新生 / 腫瘍血管内皮細胞 / 内皮細胞 / コンパニオン診断 / ビグリカン / 血管内皮細胞

Outline of Final Research Achievements

Tumor endothelial cells (TEC) from mouse xenografted tumor, especially that from highly metastatic tumor expresses high level of biglycan. Knock down of biglycan by siRNA suppressed tumor cell invasion thorough endothelial cell sheet. Co-implantation of low metastatic tumor cells with TEC developed lung metastases. This metastatic ability was abandoned by suppression of biglycan expression in TEC. Immunohistochemistry of human clinical tumors revealed specific expression of biglycan in TEC. ELISA of serum showed high biglycan level in cancer patients, especially those with metastasis.

Research Products

• [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
• [Journal Article] Heterogeneity of tumor endothelial cells and drug delivery (2016)
  • Author(s): Hida K, Maishi N, Sakurai Y, Hida Y, Harashima H
  • Journal Title: Adv Drug Deliv Rev Volume: 99 Pages: 140-147
  • DOI: 10.1016/j.addr.2015.11.008
  • Peer Reviewed
• [Journal Article] CXCL 12-CXCR7 axis is important for tumor endothelial cell angiogenic property (2015)
  • Author(s): Yamada K., Maishi N., Akiyama K., Alam Mohammad Towfik, Ohga N., Kawamoto T., Shindoh M. Takahashi N., Kamiyama T., Hida Y., Taketomi A. and Hida K.
  • Journal Title: Int J Cancer Volume: 137(12) Issue: 12 Pages: 2825-2836
  • DOI: 10.1002/ijc.29655
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Identification and expression of troponin T, a new marker on the surface of cultured tumor endothelial cells by aptamer ligand (2014)
  • Author(s): Ara MN., Hyodo M., Ohga N., Akiyama K., Hida K., Hida Y., Shinohara N., Harashima H
  • Journal Title: Cancer Med Volume: 3 Issue: 4 Pages: 825-834
  • DOI: 10.1002/cam4.260
  • Peer Reviewed / Open Access
• [Journal Article] Suprabasin as a novel tumor endothelial cell marker (2014)
  • Author(s): Alam Mohammad Towfik， Nagao-Kitamoto H., Ohga N., Akiyama K., Maishi N., Kawamoto T., Shinohara N., Taketomi A., Shindoh M., Hida Y. and Hida K.
  • Journal Title: Cancer Sci Volume: 105 Pages: 1533-1540
  • NAID: 120005539218
  • Peer Reviewed / Open Access
• [Journal Article] Identification of Novel Targets for Antiangiogenic Therapy by Comparing the Gene Expressions of Tumor and Normal Endothelial Cells (2014)
  • Author(s): Otsubo T., et al., Hida Y., Ohga N., Sato H., Kai T., Matsuki Y., Takasu H., Akiyama K., Maishi N., Kawamoto T., Shinohara N., Nonomura K., Hida K.
  • Journal Title: Cancer Sci. Volume: (印刷中) Issue: 5 Pages: 560-567
  • DOI: 10.1111/cas.12394
  • Peer Reviewed / Open Access
• [Journal Article] Heterogeneity of tumor endothelial cells (2013)
  • Author(s): Hida K., Ohga N., Akiyama K., Maishi N., Hida Y.
  • Journal Title: Cancer Sci Volume: 104 Pages: 1391-1395
  • Peer Reviewed
• [Journal Article] Application of POLARIC fluorophores in an in vivo tumor model (2013)
  • Author(s): Maishi N., Kawamoto T., Ohga N.,Yamad K., Akiyama K., Yamamoto K. , Osawa T., Hida Y. and *Hida K.
  • Journal Title: Oncol Rep Volume: 30 Pages: 1695-1700
  • Peer Reviewed
• [Presentation] Tumor endothelial cells promote metastasis (2014)
  • Author(s): Maishi N., Ohba Y., Ohga N., Akiyama K., Hamada J., Yamamoto Y., Kawamoto T., Shindoh M., Hida Y., Hida K
  • Organizer: The 18th International Vascular Biology Meeting
  • Place of Presentation: みやこめっせ（京都市）
  • Year and Date: 2014-04-14 – 2014-04-17
• [Presentation] SBSN is a novel Tumor Endothelial Cell marker (2014)
  • Author(s): Alam Mohammad Towfik, Nagao H., Ohga N., Akiyama K., Maishi N., Kawamoto T., Shinohara N., Taketomi A., Shindoh M., Hida Y., Hida K.
  • Organizer: The 18th International Vascular Biology Meeting
  • Place of Presentation: みやこめっせ（京都市）
  • Year and Date: 2014-04-14 – 2014-04-17
• [Presentation] CXCL12/CXCR7 axis is important for tumor endothelial cell angiogenic property (2014)
  • Author(s): Yamada K., Maishi N. Ohga N., Akiyama K., Kawamoto T., Alam Mohammad Towfik, Shindoh M. Takahashi N., Kamiyama T., Hida Y., Taketomi A., Hida K.
  • Organizer: The 18th International Vascular Biology Meeting
  • Place of Presentation: みやこめっせ（京都市）
  • Year and Date: 2014-04-14 – 2014-04-17
• [Presentation] 血管内皮細胞によるがん転移促進 (2013)
  • Author(s): 間石奈湖，大場雄介，大賀則孝,秋山廣輔,山本和幸，浜田淳一，川本泰輔，Alam Mohammad Towfik, 大村 瞳，進藤正信，樋田泰浩，樋田京子
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（横浜市）
• [Presentation] がん転移における腫瘍血管内皮細胞の役割 (2013)
  • Author(s): 間石奈湖，大場雄介，大賀則孝，秋山廣輔，山本和幸，浜田淳一，川本泰輔，Alam Mohammad Towfik，樋田泰浩，樋田京子
  • Organizer: 第21回日本血管生物医学会学術集会
  • Place of Presentation: 千里阪急ホテル（大阪市）
• [Remarks] 北海道大学 血管生物学教室
  • URL: http://www.den.hokudai.ac.jp/vascular-biology/
• [Remarks] 北海道大学 血管生物学教室
  • URL: http://www.den.hokudai.ac.jp/vascular-biology/index.html