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Identification of cancer stem cell niche in oral cancer and their therapeutic application

Research Project

Project/Area Number 26463035
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Surgical dentistry
Research InstitutionHokkaido University

Principal Investigator

Matsuzawa Yusuke  北海道大学, 歯学研究科, 助教 (30351620)

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)
秋山 廣輔  北海道大学, 遺伝子病制御研究所, 客員研究員 (10609100)
樋田 泰浩  北海道大学, 大学病院, 准教授 (30399919)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywordsがん幹細胞 / 腫瘍血管
Outline of Final Research Achievements

In this study, we investigated the role of tumor endothelial cells (TECs) for maintenance of cancer cell stemness. We analyzed the crosstalk of cancer stem cells (CSCs) and endothelial cells in vitro. Treatment of cultured conditioned medium of CSC-enriched cells increased the expression of TEC markers in endothelial cells. We next analyzed the signal pathways after co-culture of cancer cells with TECs. NF-kB and ERK1/2 pathways were activated in cancer cells after co-culture with high grade tumor derived TECs. In addition, colony formation was observed by co-culture with cancer cells and TECs. These data suggested that TEC-expressing molecules are involved in maintenance of stemness in cancer cells.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (42 results)

All 2017 2016 2015 2014

All Journal Article (13 results) (of which Peer Reviewed: 13 results,  Open Access: 9 results,  Acknowledgement Compliant: 1 results) Presentation (28 results) (of which Int'l Joint Research: 5 results,  Invited: 4 results) Book (1 results)

  • [Journal Article] Vasohibin-1 as a novel prognostic factor for head and neck squamous cell carcinoma2017

    • Author(s)
      Torii C., Hida Y., Shindoh M., Akiyama K., Ohga N., Maishi N., Ohiro Y., Ono M., Totsuka Y., Kitagawa Y., Tei K., Sato Y., Hida K.
    • Journal Title

      Anticancer Res

      Volume: 37 Issue: 3 Pages: 1219-1225

    • DOI

      10.21873/anticanres.11437

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Aneuploidy of murine immortalized endothelial cell line, MS12017

    • Author(s)
      Hida K., Maishi N., Dorcas Akuba-Muhyia Annan, Kondoh M., Hojo T., Umma Habiba, Ohga N., Ishikawa K, Sato M., Torii C., Yanagiya M., Morimoto M., Hida Y., Shindoh M.
    • Journal Title

      J Oral Biosci

      Volume: 59 Pages: 50-54

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Tumor endothelial cells express high pentraxin 3 levels2016

    • 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

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comparison of characteristics of mouse immortalized normal endothelial cells, MS1 and primary cultured endothelial cells2016

    • Author(s)
      Hida K., Maishi N., Torii C., Yanagiya M., Annan Akuba-Muhyia Dorcas., Morimoto M., Alam Mohammad Towfik
    • Journal Title

      Hokkaido Journal of Dental Science

      Volume: 37 Pages: 40-48

    • NAID

      120005855959

    • Related Report
      2016 Annual Research Report
    • 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

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inhibition of multidrug transporter in tumor endothelial cells enhances antiangiogenic effects of low-dose metronomic paclitaxel2015

    • 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

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dental Arch Relationship Outcomes in One- and Two-Stage Palatoplasty for Japanese Patients with Complete Unilateral Cleft Lip and Palate2015

    • Author(s)
      Tadashi Mikoya, Toyoko Shibukawa, Takafumi Susami, Yoshiaki Sato, Toshimoto Tengan, Hirotaka Katashima, Akihiko Oyama, Yusuke Matsuzawa, Yumi Ito, Emi Funayama
    • Journal Title

      Cleft Palate-Craniofacial Journal

      Volume: 52 Issue: 3 Pages: 277-286

    • DOI

      10.1597/13-285

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 上下顎に発生し自然消退した先天性エプーリスの1例2015

    • Author(s)
      澁川 統代子, 三古谷 忠, 松沢 祐介, 伊藤 裕美, 曽我部 いづみ, 鄭 漢忠
    • Journal Title

      日本口腔外科学会雑誌

      Volume: 61巻10号 Pages: 513-517

    • NAID

      130005113760

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] 大臼歯部への第三大臼歯自家移植の臨床的検討2015

    • Author(s)
      阿部結奈,松沢祐介,鄭 漢忠
    • Journal Title

      北海道歯学雑誌

      Volume: 36(2) Pages: 98-109

    • NAID

      120005725173

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Inhibition of multidrug transporter in tumor endothelial cells enhances antiangiogenic effects of low-dose metronomic paclitaxel2014

    • 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

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Identification of Tumor Endothelial Cells with High Aldehyde Dehydrogenase Activity and a Highly Angiogenic Phenotype2014

    • 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

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Suprabasin as a novel tumor endothelial cell marker2014

    • 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

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of Novel Targets for Antiangiogenic Therapy by Comparing the Gene Expressions of Tumor and Normal Endothelial Cells2014

    • 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

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 腫瘍血管内皮細胞によるBiglycanの分泌を介したがんの転移促進2017

    • Author(s)
      間石奈湖
    • Organizer
      第2回口腔医科学フロンティア研究会
    • Place of Presentation
      ZAOセンタープラザ(山形県山形市)
    • Year and Date
      2017-03-05
    • Related Report
      2016 Annual Research Report
  • [Presentation] Two cases of alveolar cleft repair using autogenous primary tooty2017

    • Author(s)
      Matsuzawa Y., Kashiwazaki H., Murata M., Abe.Y., Matsuoka M., Sogabe I., Ito Y., Mikoya T., Tei K.
    • Organizer
      13th International Congress of Cleft Lip & Palate and Related Craniofacial Anomalies
    • Place of Presentation
      Chennai(India)
    • Year and Date
      2017-02-08
    • Related Report
      2016 Annual Research Report
  • [Presentation] Correlation between CXCR7 expression of blood vessels and clinicopathological features in oral squamous cell carcinoma2016

    • Author(s)
      柳谷美沙,間石奈湖,鳥居ちさほ,樋田泰浩,大賀則孝,鄭 漢忠,進藤正信,北川善政,樋田京子
    • Organizer
      第24回日本血管生物医学会学術集会
    • Place of Presentation
      長崎ブリックホール(長崎県長崎市)
    • Year and Date
      2016-12-10
    • Related Report
      2016 Annual Research Report
  • [Presentation] Tumor endothelial cells acquire drug resistance by exosomal-miR derived from high metastatic tumor2016

    • Author(s)
      3.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
    • Place of Presentation
      Boston(America)
    • Year and Date
      2016-11-02
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Tumor endothelial cells in high metastatic tumors promote metastasis via biglycan2016

    • Author(s)
      4.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(America)
    • Year and Date
      2016-11-02
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 腫瘍血管内皮細胞によるがん転移促進2016

    • Author(s)
      間石奈湖,樋田京子
    • Organizer
      第75回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-10-07
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] ブロック型脱灰象牙質移植による歯槽堤増生を行いインプラントを埋入した1例2016

    • Author(s)
      松沢祐介,村田勝,阿部結奈,長太一
    • Organizer
      第46回日本口腔インプラント学会学術大会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2016-09-17
    • Related Report
      2016 Annual Research Report
  • [Presentation] 活性酸素が腫瘍血管内皮細胞に及ぼす影響2016

    • Author(s)
      間石 奈湖、樋田 京子
    • Organizer
      第 69 回日本酸化ストレス学会学術集会
    • Place of Presentation
      仙台国際センター(宮城県仙台市)
    • Year and Date
      2016-08-31
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 腫瘍血管内皮細胞によるbiglycanの分泌を介したがんの転移促進2016

    • Author(s)
      間石奈湖,秋山廣輔,大賀則孝,浜田淳一,樋田京子
    • Organizer
      第25回日本がん転移学会学術集会・総会
    • Place of Presentation
      米子コンベンションセンター(鳥取県米子市)
    • Year and Date
      2016-07-21
    • Related Report
      2016 Annual Research Report
  • [Presentation] 瘍血管内皮細胞によるがん転移促進2016

    • Author(s)
      間石奈湖
    • Organizer
      第12回北海道癌免疫制御研究会
    • Place of Presentation
      メルキュールホテル札幌 (北海道札幌市)
    • Year and Date
      2016-07-09
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 乳歯の自家脱灰象牙質顆粒を用いた顎裂部の再建2016

    • Author(s)
      松沢祐介,村田勝,松岡真琴,曾我部いづみ,伊藤裕美、三古谷忠、鄭漢忠
    • Organizer
      第40回日本口蓋裂学会総会・学術集会
    • Place of Presentation
      ナレッジキャピタル コングレコンベンションセンター(大阪府大阪市)
    • Year and Date
      2016-05-27
    • Related Report
      2016 Annual Research Report
  • [Presentation] Clinical study on autotransplantation of teeth in patients aged over 60 years of age2016

    • Author(s)
      Matsuzawa Y., Abe Y., Tei K.
    • Organizer
      1st congress on Tooth transplantation
    • Place of Presentation
      Sopot(Poland)
    • Year and Date
      2016-05-22
    • Related Report
      2016 Annual Research Report
  • [Presentation] Tumor Endothelial Cells Promote Metastasis via Biglycan2016

    • Author(s)
      Maishi N.
    • Organizer
      Keystone Symposia on Molecular and Cellular Biology
    • Place of Presentation
      Breckenridge, Colorado, USA
    • Year and Date
      2016-03-30
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 腫瘍分泌小胞miRNAによる血管内皮の薬剤耐性誘2016

    • Author(s)
      鳥居ちさほ,間石奈湖,樋田京子
    • Organizer
      第2回血管生物若手研究会
    • Place of Presentation
      仙台 東北大学
    • Year and Date
      2016-03-04
    • Related Report
      2015 Research-status Report
  • [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 名古屋国際会議場
    • Year and Date
      2015-10-10
    • Related Report
      2015 Research-status Report
  • [Presentation] 高転移性腫瘍miRNA はIL-6 ならびにALDH の発現亢進を介して血管内皮に薬剤耐性を誘導する2015

    • Author(s)
      鳥居ちさほ,秋山廣輔,川本泰輔,間石奈湖,鄭漢忠,戸塚靖則,進藤正信,樋田泰浩,南敬,小坂展慶,落谷孝広,樋田京子
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋 名古屋国際会議場
    • Year and Date
      2015-10-10
    • Related Report
      2015 Research-status Report
  • [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 名古屋国際会議場
    • Year and Date
      2015-10-08
    • Related Report
      2015 Research-status Report
  • [Presentation] Tumor endothelial cells promote metastasis via biglycan secretion2015

    • 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
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Modification of the monocortical mandibular bone grafting for the reconstruction of alveolar cleft2015

    • Author(s)
      Yusuke Matsuzawa
    • Organizer
      12th National Conference on Oral Maxillofacial Surgery in Conjunction with 1st China-Japan Joint Conference on Maxillofacial Surgery
    • Place of Presentation
      Shanghai
    • Year and Date
      2015-09-26
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Tumor Endothelial cell-secreted protein activates a DNA damage response2015

    • Author(s)
      Annan Dorcas A., 間石奈湖,北條敬之,鳥居ちさほ,Mohammad T Alam.,Habiba Umma,樋田泰浩,樋田京子
    • Organizer
      第112回北海道癌談話会例会
    • Place of Presentation
      札幌 北海道大学
    • Year and Date
      2015-09-12
    • Related Report
      2015 Research-status Report
  • [Presentation] 高転移性腫瘍miRによらう血管内皮におけるIL-6を介した薬剤耐性誘導2015

    • Author(s)
      鳥居ちさほ,秋山廣輔,川本泰輔,間石奈湖,Alam Mohammad Towfik,鄭 漢忠,戸塚靖則,進藤正信,樋田泰浩,南 敬,小坂展慶,落谷孝広,樋田京子
    • Organizer
      第112回北海道癌談話会例会
    • Place of Presentation
      札幌 北海道大学
    • Year and Date
      2015-09-12
    • Related Report
      2015 Research-status Report
  • [Presentation] Suprabasin as a novel tumor endothelial cell marker2015

    • Author(s)
      Alam Mohammad Towfik,Nagao-Kitamoto H., Ohga N., Akiyama K., Maishi N., Kawamoto T, Shinohara N., Taketomi A., Shindoh M, Hida Y, Hida K
    • Organizer
      第26回日本臨床口腔病理学会総会・学術大会
    • Place of Presentation
      札幌 北海道大学
    • Year and Date
      2015-07-31
    • Related Report
      2015 Research-status Report
  • [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
      札幌 北海道大学
    • Year and Date
      2015-07-31
    • Related Report
      2015 Research-status Report
  • [Presentation] 高転移性腫瘍miRNAはIL-6ならびにALDHの発現亢進を介して血管内皮に薬剤耐性を誘導する2015

    • Author(s)
      鳥居ちさほ,秋山廣輔,川本泰輔,間石奈湖,鄭 漢忠,戸塚靖則,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
      札幌 北海道大学
    • Year and Date
      2015-07-31
    • Related Report
      2015 Research-status Report
  • [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
      札幌 北海道大学
    • Year and Date
      2015-07-31
    • Related Report
      2015 Research-status Report
  • [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
    • Organizer
      第24回日本がん転移学会学術集会・総会
    • Place of Presentation
      大阪 シティプラザ大阪
    • Year and Date
      2015-07-23
    • Related Report
      2015 Research-status Report
  • [Presentation] 嚢胞性疾患を伴った低位埋伏智歯を用いた歯の移植の1例2015

    • Author(s)
      松沢祐介,阿部結奈,鄭漢忠
    • Organizer
      第41回公益社団法人日本口腔外科学会北日本支部学術集会
    • Place of Presentation
      札幌 札幌プリンスホテル
    • Year and Date
      2015-06-28
    • Related Report
      2015 Research-status Report
  • [Presentation] Tumor endothelial cells instigate metastasis of indolent tumors2015

    • Author(s)
      Maishi N., Hida K
    • Organizer
      Spring Special Symposium of the Japanese Vascular Biology and Medicine Organization
    • Place of Presentation
      Osaka, Japan
    • Year and Date
      2015-05-13
    • Related Report
      2015 Research-status Report
    • Invited
  • [Book] 別冊BIO Clinica 慢性炎症と疾患~慢性炎症とがん2016

    • Author(s)
      樋田京子,大賀則孝,間石奈湖,秋山廣輔,樋田泰浩
    • Publisher
      北隆館
    • Related Report
      2015 Research-status Report

URL: 

Published: 2014-04-04   Modified: 2018-03-22  

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