The heterogeneity of tumor endothelial cells of hepatocellular carcinoma and the application to novel molecular targeted therapies

• Project/Area Number: 25670564
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Hokkaido University
• Principal Investigator: TAKAHASHI Norihiko 北海道大学, 大学病院, 准教授 (30399894)
• Co-Investigator(Kenkyū-buntansha): HONMA Shigenori 北海道大学, 北海道大学病院, 助教 (30533674) ; SHIMOKUNI Tatsushi 北海道大学, 北海道大学病院, 特任教授 (30596458) ; OHGA Noritaka 北海道大学, 大学院歯学研究科, 助教 (40548202) ; SAKIHAMA Hideyasu 北海道大学, 北海道大学病院, 特任助教 (50533676) ; TAKETOMI Akinobu 北海道大学, 大学院医学研究科, 教授 (70363364) ; 神山 俊哉 北海道大学, 医学(系)研究科(研究院), 准教授 (80322816)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 腫瘍血管新生 / 腫瘍血管内皮の不均一性

Outline of Final Research Achievements

We have reported that tumor endothelial cells are heterogeneous depending on tumor malignancy. In this study, we tried to evaluate the difference of tumor endothelial cells of hepatocellular carcinoma, in order to develop novel molecular for targeting liver cancer. We identified a marker that is highly expressed in poorly differentiated cancer compared to well-differentiated cancer and show that this molecule plays an important role for tumor cell metastasis. These results suggested that tumor endothelial cell may be involved in tumor metastasis in malignant hepatocellular carcinoma.

Research Products

• [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 Pages: 2825-2836
  • Peer Reviewed
• [Journal Article] Inhibition of multidrug transporter in tumor endothelial cells enhances antiangiogenic effects of low-dose metronomic paclitaxel. (2015)
  • Author(s): 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) Pages: 572-580
  • Peer Reviewed
• [Journal Article] Identification of Tumor Endothelial Cells with High Aldehyde Dehydrogenase Activity and a Highly Angiogenic Phenotype (2014)
  • Author(s): 2.Ohmura-Kakutani H., Akiyama K., Maishi N., Ohga N., Hida Y., Kawamoto T., Iida J., Shindoh M., Tsuchiya K., Shinohara N., *Hida K
  • Journal Title: PLoS ONE Volume: 9(12) Issue: 12 Pages: e113910-e113910
  • DOI: 10.1371/journal.pone.0113910
  • NAID: 120005540289
  • 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
• [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