Application of biglyan as tumor biomarker of oral cancer

• Project/Area Number: 25462909
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pathobiological dentistry/Dental radiology
• Research Institution: Hokkaido University
• Principal Investigator: Ono Mitsunobu 北海道大学, 大学病院, 講師 (50281829)
• Co-Investigator(Kenkyū-buntansha): OHGA Noritaka 北海道大学, 大学院歯学研究科, 助教 (40548202) ; KITAMURA Tetsuya 北海道大学, 大学院歯学研究科, 助教 (00451451) ; SHINDOH Masanobu 北海道大学, 大学院歯学研究科, 教授 (20162802)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); 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); Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 腫瘍血管内皮細胞 / Biglycan / プロテオグリカン / 腫瘍マーカー

Outline of Final Research Achievements

We focused on biglycan which is proteoglycan and a published-tumor endothelial markers. Since the function of biglycan has not been fully evaluated, we addressed the role of biclycan in tumor vasculature in oral cancer in this study. We showed that biglycan is involved in tumor endothelial cell migration. The biglycan plasma level was elevated in cancer patients compared to that in normal volunteer. Finally, we tried to establish the system for targeting biglycan in tumor endothelial cells using drug delivery system which contains biglycan siRNA.

Research Products

• [Journal Article] Evaluation of the level of progression of extracapsular spread for cervical lymph node metastasis in oral squamous cell carcinoma. (2016)
  • Author(s): Yamada S, Yanamoto S, Otani S, Hasegawa T, Miyakoshi M, Minamikawa T, Ohga N, Kamata T, Komori T, Kitagawa Y, Kurita H, Umeda M.
  • Journal Title: Int J Oral Maxillofac Surg Volume: 45(2) Issue: 2 Pages: 141-6
  • DOI: 10.1016/j.ijom.2015.09.005
  • 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
• [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] 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] RNAi-mediated gene knockdown and anti-angiogenic therapy of RCCs using a cyclic RGD-modified liposomal-siRNA system (2014)
  • Author(s): Yu Sakurai, Hiroto Hatakeyama, Yusuke Sato, Mamoru Hyodo, Hidetaka Akita, Noritaka Ohga, Kyoko Hida, Hideyoshi Harashima
  • Journal Title: J. Control. Release Volume: 173 Pages: 110-118
  • DOI: 10.1016/j.jconrel.2013.10.003
  • Peer Reviewed
• [Journal Article] Hypoxia-induced reactive oxygen species cause chromosomal abnormalities in endothelial cells in the tumor microenvironment (2013)
  • Author(s): Kondoh M., Ohga N., Akiyama K., Hida Y., Maishi N., Alam Mohammad Towfik, Inoue N., Shindoh M. and Hida K
  • Journal Title: PLoS ONE Volume: 8(11) Issue: 11 Pages: e80349-e80349
  • DOI: 10.1371/journal.pone.0080349
  • NAID: 120005367415
  • Peer Reviewed
• [Journal Article] Lysyl oxidase secreted by tumour endothelial cells Promotes angiogenesis and metastasiso (2013)
  • Author(s): Osawa T., et al., Ohga N., Akiyama K., Hida Y., Kitayama K., Kawamoto T, , Yamamoto K., Maishi N., Kondoh M., Onodera Y., Fujie M., Nonomura K., Shindoh M., Hida K.
  • Journal Title: Br. J. Cancer Volume: 109(8) Issue: 8 Pages: 2237-2247
  • DOI: 10.1038/bjc.2013.535
  • Peer Reviewed
• [Journal Article] A liposomal delivery system that targets liver endothelial cells based on a new peptide motif present in the ApoB-100 sequence (2013)
  • Author(s): Akhter A, Hayashi Y, Sakurai Y, Ohga N, Hida K, Harashima H.
  • Journal Title: Int J Pharm. Volume: 456 Issue: 1 Pages: 195-201
  • DOI: 10.1016/j.ijpharm.2013.07.068
  • NAID: 120005394547
  • Peer Reviewed
• [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 Issue: 11 Pages: 1391-1395
  • DOI: 10.1111/cas.12251
  • Peer Reviewed
• [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: Messe Wien Exhibition & Congress Centre, 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
  • Place of Presentation: 北海道大学（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
  • Place of Presentation: 北海道大学（北海道札幌市）
  • Year and Date: 2015-07-31
• [Presentation] 活性酸素種による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，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26回日本臨床口腔病理学会総会
  • Place of Presentation: 北海道大学（北海道札幌市）
  • Year and Date: 2015-07-31
• [Presentation] The feasibility of supraomohyoid neck dissection for node-positive oral squamous cell carcinoma. (2013)
  • Author(s): Ono M., Ohiro Y., Kuribayashi K., Ashikaga Y., Tei K.
  • Organizer: 21st International Conference on Oral and Maxillofacial Surgery
  • Place of Presentation: Palau de Congressos de Catalunya (Barcelona, Spain)
• [Presentation] 下顎歯肉癌の顎骨浸潤と臨床像
  • Author(s): 小野貢伸、進藤正信、鄭 漢忠
  • Organizer: 第32回日本口腔腫瘍学会
  • Place of Presentation: 札幌コンベンションセンター（札幌市）
  • Invited
• [Presentation] Vasohibin-1 as a novel prognostic factor in oral squamous cell carcinoma
  • Author(s): Torii C, Ohga N, Akiyama K, Maishi N, Hojo T, Ohiro Y，Ono M, YTotsuka Y，Tei K，Hida Y，Shindoh M, Sato Y, Hida K
  • Organizer: 第72回日本癌学会総会
  • Place of Presentation: パシフィコ横浜（横浜市）
• [Book] 別冊BIO Clinica 慢性炎症と疾患～慢性炎症とがん，5(1) (2016)
  • Author(s): 樋田京子，大賀則孝，間石奈湖，秋山廣輔，樋田泰浩
  • Total Pages: 172
  • Publisher: 北隆館