Overcome the drug resistance by targeting tumor endothelial markers

• Project/Area Number: 26861540
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Morphological basic dentistry
• Research Institution: Hokkaido University
• Principal Investigator: Alam Mohammad Towfik 北海道大学, 歯学研究科, 学術研究員 (60641694)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 腫瘍血管内皮細胞 / がん幹細胞 / 薬剤抵抗性 / 腫瘍血管内皮細胞、 / 血管新生阻害療法

Outline of Final Research Achievements

In this study, to identify tumor endothelial marker (TEC marker) that is involved in drug resistance, drug sensitivity to anti-cancer drug was analyzed using siRNA or inhibitor of TEC markers. The inhibitor of p-glycoprotein encoded by MDR-1 gene, enhanced sensitivity to paclitaxel, in vitro and in vivo. These results suggested that inhibition of TEC markers are possible strategy to overcome drug resistance.

Research Products

• [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 J. Dent. Sci. Volume: 37 Pages: 40-48
  • Peer Reviewed
• [Journal Article] Tumour endothelial cells in high metastatic tumours promote metastasis via epigenetic dysregulation of biglycan. (2016)
  • Author(s): N. Maishi, Y. Ohba, K. Akiyama, N. Ohga, J.I. Hamada, H. Nagao-Kitamoto, M. Alam, K. Yamamoto, T. Kawamoto, N. Inoue, A. Taketomi, M. Shindoh, Y. Hida and K. Hida.
  • Journal Title: Sci. Rep. Volume: 6 Issue: 1 Pages: 28039-28039
  • DOI: 10.1038/srep28039
  • NAID: 120005819304
  • Peer Reviewed / Open Access
• [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] Inhibition of multidrug transporter in tumor endothelial cells enhances antiangiogenic effects of low-dose metronomic paclitaxel (2015)
  • Author(s): 1.Akiyama K., Maishi N., Ohga N., Hida Y., Ohba Y., Alam Mohammad Towfik, Kawamoto T., Ohmura H., Yamada K., Torii C., Shindoh M. and *Hida K.
  • Journal Title: Am J Pathol Volume: 185(2) Issue: 2 Pages: 572-580
  • DOI: 10.1016/j.ajpath.2014.10.017
  • Peer Reviewed / Open Access
• [Journal Article] Suprabasin as a novel tumor endothelial cell marker (2014)
  • Author(s): 3.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(12) Issue: 12 Pages: 1533-1540
  • DOI: 10.1111/cas.12549
  • NAID: 120005539218
  • Peer Reviewed / Open Access
• [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 国際学会
  • Place of Presentation: Boston, Massachusetts, USA
  • Year and Date: 2016-11-02
  • Int'l Joint Research
• [Presentation] Tumor endothelial cells in high metastatic tumors promote metastasis via biglycan, (2016)
  • Author(s): Maishi N., Ohba Y., Akiyama K., Ohga N., Hamada J., Nagao-Kitamoto H., Mohammad Towfik Alam, Shindoh M., Hida Y. Hida K.
  • Organizer: The 19th International Vascular Biology Meeting
  • Place of Presentation: Boston, Massachusetts, USA
  • Year and Date: 2016-11-02
  • Int'l Joint Research
• [Presentation] Tumor endothelial cells promote metastasis via biglycan secretion (2016)
  • Author(s): Maishi N., Ohba Y., Akiyama K., Ohga N., Hamada J., Mohammad Towfik Alam, Shindoh M., Hida Y., Hida K
  • Organizer: Tenth AACR-JCA Joint Conference “Breakthroughs in Cancer Research: From Biology to Therapeutics”
  • Place of Presentation: Maui (USA)
  • Year and Date: 2016-02-17
  • Int'l Joint Research
• [Presentation] ROS によるbiglycan 発現誘導を介した腫瘍血管内皮細胞の血管新生能亢進 (2015)
  • Author(s): 北條敬之，間石奈湖，Mohammad T Alam，秋山廣輔，大賀則孝，進藤正信，樋田泰浩，藤澤俊明，樋田京子
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場（愛知県・名古屋市）
  • Year and Date: 2015-10-10
• [Presentation] 腫瘍血管内皮細胞はbiglycan の分泌を介してがんの転移を促進する (2015)
  • Author(s): 間石奈湖，大場雄介，秋山廣輔，大賀則孝，浜田淳一，北本(永尾）宗子，Mohammad Alam T.，進藤正信，樋田泰浩，樋田京子
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場（愛知県・名古屋市）
  • Year and Date: 2015-10-08
• [Presentation] Tumor endothelial cells promote metastasis via biglycan secretion (2015)
  • Author(s): Maishi N., Ohba Y., Akiyama K., Ohga N., Hamada J., Mohammad Towfik Alam, Shindoh M., Hida Y., Hida K
  • Organizer: The European Cancer Congress 2015
  • Place of Presentation: Vienna (Austria)
  • Year and Date: 2015-09-27
  • Int'l Joint Research
• [Presentation] 腫瘍血管内皮細胞はbiglycanの分泌を介してがんの転移を促進する (2015)
  • Author(s): 間石奈湖，大場雄介，秋山廣輔，大賀則孝，浜田淳一，北本宗子，Alam Mohammad Towfik，進藤正信，樋田泰浩，樋田京子
  • Organizer: 第26回日本臨床口腔病理学会総会・学術大会
  • Place of Presentation: 北海道大学学術交流会館（北海道・札幌市）
  • Year and Date: 2015-07-31
• [Presentation] Suprabasin as a novel tumor endothelial cell marker (2015)
  • Author(s): Alam Mohammad Towfik，Nagao-Kitamoto H., Ohga N., Akiyama K., Maishi N., Shinohara N., Taketomi A.
  • Organizer: 第26回日本臨床口腔病理学会総会・学術大会
  • Place of Presentation: 北海道大学学術交流会館（北海道・札幌市）
  • Year and Date: 2015-07-31
• [Presentation] P-gp inhibitor enhances antiangiogenic activity in metronomic chemotherapy (2014)
  • Author(s): Akiyama K., Ohga N., Hida Y., Maishi N., Alam Mohammad Towfik, Kawamoto T., Omura H., Yamada Y., Torii C., Shindoh M., Ohba Y., Hida K.
  • Organizer: The 18th International Vascular Biology Meeting
  • Place of Presentation: みやこめっせ(京都府・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(京都府・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(京都府・京都市）
  • Year and Date: 2014-04-14 – 2014-04-17
• [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/