Development of new treatment strategy targeting for vascular niche of oral cancer stem cell

• Project/Area Number: 25463106
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Hokkaido University
• Principal Investigator: OHIRO Yoichi 北海道大学, 歯学研究科(研究院), 講師 (40301915)
• Co-Investigator(Kenkyū-buntansha): AKIYAMA Kousuke 北海道大学, 遺伝子制御研究所, 客員研究員 (10609100) ; TEI Kanchu 北海道大学, 歯学研究科(研究院), 教授 (80180066) ; 進藤 正信 北海道大学, 歯学研究科(研究院), 教授 (20162802)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 腫瘍血管内皮細胞 / がん幹細胞 / 薬剤抵抗性

Outline of Final Research Achievements

Cancer stem cells (CSC) or matured cancer cells were fractionated from cancer cell lines. Tumor endothelial cells (TEC) were separated from transplanted tumors in vivo model. CSC were co-cultured with TEC or treated with TEC conditioned media (TEC-TM). These experiments revealed that activation of survival signal such as Akt or NF-kB, alteration of expression levels of CSC markers and inhibitory effect against apopotosis were induced in CSC. Furthermore, co-cultivation of CSC with TEC separated from highly metastatic tumor induce the formation of large sphenoid or inhibitory effect for anoikis by TEC.

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(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): 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 Pages: 572-580
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Cytoplasmic expression of HuR may be a valuable diagnostic tool for determining the potential for malignant transformation of oral verrucous borderline lesions (2014)
  • Author(s): Habiba U., Kitamura T., Yanagawa-Matsuda A., Hida K., Higashino F., Ohiro Y., Totsuka Y. and Shindoh M
  • Journal Title: Oncology Reports Volume: 31 Issue: 4 Pages: 1547-1554
  • DOI: 10.3892/or.2014.3017
  • 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., 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: 105 Pages: 560-567
  • Peer Reviewed / Open Access
• [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] 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)
  • 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
• [Presentation] 反復処置法による角化嚢胞性歯原性腫瘍の治療 (2015)
  • Author(s): 大廣 洋一
  • Organizer: 第60回（公社）日本口腔外科学会総会・学術大会
  • Place of Presentation: 名古屋国際会議場（愛知県，名古屋）
  • Year and Date: 2015-10-16
• [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）
  • Year and Date: 2015-10-08
• [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）
  • 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: 2015-09-25
• [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）
  • Year and Date: 2015-07-29
• [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）
  • Year and Date: 2015-07-29
• [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・学術大会
  • Place of Presentation: 北海道大学学術交流会館（北海道，札幌）
  • Year and Date: 2015-07-29
• [Presentation] エナメル上皮腫に対する反復処置法について (2015)
  • Author(s): 大廣 洋一
  • Organizer: 第69回NPO法人日本口腔科学会学術集会
  • Place of Presentation: 大阪国際会議場（大阪府，大阪）
  • Year and Date: 2015-05-13
• [Presentation] 反復処置法による角化嚢胞性歯原性腫瘍の治療 (2014)
  • Author(s): 大廣 洋一
  • Organizer: 第59回（公社）日本口腔外科学会総会・学術大会
  • Place of Presentation: 幕張メッセ（千葉県、千葉）
  • Year and Date: 2014-10-17 – 2014-10-19
• [Presentation] Locoregional control in advanced resectable oral squamous cell carcinoma by concurrent preoperative chemoradiotherapy with Docetaxel and Cisplatin (2014)
  • Author(s): OHIRO, Y., KURIBAYASHI, K, ASHIKAGA Y., ONO M., TOTSUKA, Y., TEI, K.
  • Organizer: The 22th European Association for Cranio-Maxillo-Facial Surgery
  • Place of Presentation: Plague（Czechoslovakia）
  • Year and Date: 2014-09-23 – 2014-09-26
• [Presentation] Vasohibin-1 as a novel prognostic factor in oral squamous cell carcinoma (2014)
  • Author(s): Torii C., Ohga N., Akiyama K., Maishi N., Hojo T., Ohiro Y., Ono M., Totsuka Y., Kitagawa Y., Tei K., Hida Y., Shindoh M., Sato Y., Hida K
  • Organizer: The 18th International Vascular Biology Meeting
  • Place of Presentation: みやこめっせ（京都府、京都）
  • Year and Date: 2014-04-14 – 2014-04-17
• [Presentation] 局所進行口腔癌における術前DOC・ CDDP併用放射線療法の有用性. (2014)
  • Author(s): 大廣洋一，栗林和代，足利雄一，小野貢伸，進藤正信，鄭 漢忠
  • Organizer: 第３２回日本口腔腫瘍学会総会・学術大会
  • Place of Presentation: 札幌コンベンションセンター（札幌市）
• [Presentation] Dredging Method－A Conservative Approach for the Treatment of Keratocystic Odontogenic Tumor. (2014)
  • Author(s): Ohiro Y, Totsuka Y, Tei K
  • Organizer: 第26回台湾口腔外科学会学術大会
  • Place of Presentation: エバーグリーンホテル（台湾）
• [Presentation] Vasohibin-1 as a novel prognostic factor in oral squamous cell carcinoma. (2013)
  • Author(s): Chisaho Torii, Noritaka Ohga, Kosuke Akiyama, Nako Maishi, Takayuki Hojo, Yoichi Ohiro， Mitsunobu Ono, Yasunori Totsuka，Kanchu Tei，Yasuhiro Hida，Masanobu Shindoh , Yasufumi Sato, Kyoko Hida
  • 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）
• [Book] 腫瘍血管内皮細胞の多様性 (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: 7
  • Publisher: 北隆館