Development of next generation lung cancer treatment targeting tumor vascular specific markers

• Project/Area Number: 15H04941
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Respiratory 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): 間石 奈湖 北海道大学, 遺伝子病制御研究所, 助教 (00632423) ; 加賀 基知三 北海道大学, 大学病院, 講師 (80224335) ; 松居 喜郎 北海道大学, 大学病院, 教授 (90219379) ; 秋山 廣輔 北海道大学, 遺伝子病制御研究所, 客員研究員 (10609100)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000); Fiscal Year 2017: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2016: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2015: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
• Keywords: 血管新生 / 肺癌 / 腫瘍血管 / 創薬 / 腫瘍血管新生

Outline of Final Research Achievements

Lung cancer patients showed higher serum Biglycan (BGN) than healthy control. In lung cancer patients, BGN level correlated with tumor size and invasiveness. Adenocarcinoma was associated with lower BGN than other lung cancers. In tumor tissue, BGN expression was observed in tumor endothelial cells. BGN expression in tissue correlated with serum BGN level. BGN expression in tumor tissue correlated with shorter overall survival.
Large number of mouse tumor and normal endothelial cells were used for tumor endothelial cell specific inhibitor screening. We could find several hit compounds.
We successfully induce SV40 and hTERT genes to human endothelial cells and grow them in long term.

Research Products

• [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] 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] Comparative genetic analysis of a rare synchronous collision tumor composed of malignant pleural mesothelioma and primary pulmonary adenocarcinoma. (2016)
  • Author(s): Naka T, Hatanaka Y, Marukawa K, Okada H, Hatanaka KC, Sakakibara-Konishi J, Oizumi S, Hida Y, Kaga K, Mitsuhashi T, Matsuno Y
  • Journal Title: Diagn Pathol Volume: 11 Issue: 1 Pages: 1-6
  • DOI: 10.1186/s13000-016-0488-0
  • NAID: 120005766752
  • Peer Reviewed / Open Access
• [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
• [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: 19th International Vascular Biology Meeting
  • 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: 19th International Vascular Biology Meeting
  • Int'l Joint Research
• [Presentation] P-glycoprotein expression dynamics in tumor blood vessels of urothelial carcinoma during chemotherapy,” has been accepted for presentation at Vascular Biology (2016)
  • Author(s): Kikuchi H., Maishi N., Akiyama K., Morimoto M., Yanagiya M., Miyajima N., Tuchiya K., Maruyama S., Abe T., Hida Y., Harabayashi T., Ameda K., Matsumoto R., Kashiwagi A., Demura T., Tsuda M., Tanaka S., Matsuno Y., Shinohara N., Hida K
  • Organizer: 19th International Vascular Biology Meeting
  • Int'l Joint Research
• [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
  • Place of Presentation: Vienna, Austria
  • Int'l Joint Research
• [Book] 実験医学増刊「がん微小環境と標的治療」 (2015)
  • Author(s): 樋田京子, 間石奈湖，樋田泰浩
  • Total Pages: 210
  • Publisher: 羊土社