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Elucidation of cytokine network in oral squamous cell carcinoma stem cell niche, and its application to diagnosis/treatment

Research Project

Project/Area Number 24390456
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Surgical dentistry
Research InstitutionHiroshima University

Principal Investigator

OKAMOTO TETSUJI  広島大学, 医歯薬保健学研究院, 教授 (00169153)

Co-Investigator(Kenkyū-buntansha) HAYASHIDO Yasutaka  広島大学, 病院, 講師 (70243251)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥18,330,000 (Direct Cost: ¥14,100,000、Indirect Cost: ¥4,230,000)
Fiscal Year 2014: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2012: ¥8,450,000 (Direct Cost: ¥6,500,000、Indirect Cost: ¥1,950,000)
Keywords口腔扁平上皮癌細胞 / 癌幹細胞 / CD133 / CD44 / side population / rBC2LCN / 無血清培養 / sphere形成 / 口腔扁平上皮癌 / Side population / 未分化マーカー / 口腔癌 / 無血清浮遊培養 / sphere形成能 / HIF-1a / side population細胞 / 口腔がん / 口腔癌幹細胞ニッチ / Sp細胞 / サイトカインネットワーク / 細胞増殖因子
Outline of Final Research Achievements

In this study, we aimed to establish a new diagnosis and treatment that target cancer stem cells along with the elucidation of the carcinogenesis of oral squamous cell carcinoma (OSCC). For that, the cancer stem cells of OSCC, will be separated, and identified in serum-free culture. Then the niche mechanism of OSCC will be clarified. We examined the usefulness of CD133(+), Sp and rBC2LCN that is specifically expressed in ES / iPSCs, as a stem cell marker of OSCC.
As a result, positive cell ratio of CD133 (+), rBC2LCN (+), and Sp is 0.5%, 2%, and 1%, respectively. These cells exhibited a high sphere forming ability in suspension culture. EGF and sonic hedgehog induces sphere forming ability. Sp showed resistance to anti-cancer drug and high tumorigenicity. rBC2LCN I was considered to be useful as a novel OSCC stem cell marker.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (44 results)

All 2015 2014 2013 2012

All Journal Article (18 results) (of which Peer Reviewed: 18 results,  Open Access: 6 results,  Acknowledgement Compliant: 2 results) Presentation (25 results) (of which Invited: 2 results) Book (1 results)

  • [Journal Article] Comparison of the prognosis of bisphosphonate-related osteonecrosis of the jaw caused by oral and intravenous bisphosphonates.2015

    • Author(s)
      Shintani T, Hayashido Y, Mukasa H, Akagi E, Hoshino M, Ishida Y, Hamana T, Okamoto K, Kanda T, Koizumi K, Yoshioka Y, Tani R, Toratani S, Okamoto T
    • Journal Title

      Int J Oral Maxillofac Surg

      Volume: in press Issue: 7 Pages: 125-133

    • DOI

      10.1016/j.ijom.2015.03.013

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Anti-EGFR monoclonal antibody 12-93 inhibits the growth of human salivary adenocarcinoma via sub-G1 arrest and induction of apoptosis2014

    • Author(s)
      Yamamoto N, Toratani S, Okamoto T.
    • Journal Title

      J Oral Maxillofac Surg, Med, Pathol

      Volume: 26 Issue: 2 Pages: 183-187

    • DOI

      10.1016/j.ajoms.2013.08.007

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Generation of human induced pluripotent stem (iPS) cells in serum- and feeder-free defined culture and TGF-β1 regulation of pluripotency2014

    • Author(s)
      Yamasaki S, Taguchi Y, Mukasa H, Shimamoto A, Tahara T, Okamoto T.
    • Journal Title

      PlosONE

      Volume: Jan(29);9(1)

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] 1α,25(OH)2D3 inhibits FGF-2 release from oral squamous cell carcinoma cells through downregulation of HBp17/FGFBP-12014

    • Author(s)
      S. N. Zawani B. Rosli, Shintani T. Hayashido Y, Toratani S, Okamoto T.
    • Journal Title

      In Vitro Cell. Devel. Biol.-Anim

      Volume: Oct;50(9) Issue: 9 Pages: 802-806

    • DOI

      10.1007/s11626-014-9787-5

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Overexpression of integrin αv facilitates proliferation and invasion of oral squamous cell carcinoma cells via MEK/ERK signaling pathway that is activated by interaction of integrin αvβ8 with type Ⅰ collagen2014

    • Author(s)
      Hayashido Y, Kitano H, Sakaue T, Fujii T, Suematsu M, Sakurai S, Okamoto T
    • Journal Title

      Int J Oncol

      Volume: 45(5) Issue: 5 Pages: 1875-1882

    • DOI

      10.3892/ijo.2014.2642

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Generation of Human induced pluripotent Stem (iPS) cells in serum- and feeder-free defined culture and TGF-β1 regulation of pluripotency2014

    • Author(s)
      Yamasaki S, Taguchi Y, Shimamoto A, Mukasa H, Tahara H, Okamoto T.
    • Journal Title

      PLoS One

      Volume: 9(1) Issue: 1 Pages: 1-13

    • DOI

      10.1371/journal.pone.0087151

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Long-term serial cultivation of mouse induced pluripotent stem cells in serum-free and feeder-free defined medium2013

    • Author(s)
      Yamasaki S, Nabeshima K, Sotomaru Y, Taguchi Y, Mukasa H, Furue MK, Sato JD, Okamoto T
    • Journal Title

      Int J Dev Biol

      Volume: 57(9-10) Issue: 9-10 Pages: 715-724

    • DOI

      10.1387/ijdb.130173to

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Biomedical advances from tissue culture.2013

    • Author(s)
      Okamoto T., Sato JD., Barnes DW. And Sato GH.
    • Journal Title

      Cytotechnology

      Volume: 65(6), Issue: 6 Pages: 967-971

    • DOI

      10.1007/s10616-013-9591-1

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ectomesenchymal chondromyxoid tumor of the tongue: insights on histogenesis.2013

    • Author(s)
      Yoshioka Y, , Toratani S, Okamoto T. 他3名
    • Journal Title

      Oral Surg Oral Med Oral Pathol Oral Radiol.

      Volume: Feb;115(2) Issue: 2 Pages: 233-240

    • DOI

      10.1016/j.oooo.2012.11.008

    • Related Report
      2013 Annual Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ameloblastic carcinoma, secondary type, of the mandible: a case report.2013

    • Author(s)
      Yoshioka Y, Toratani S, Ogawa I, Okamoto T.
    • Journal Title

      J Oral Maxillofac Surg.

      Volume: Jan;71(1) Issue: 1 Pages: 58-62

    • DOI

      10.1016/j.joms.2012.09.005

    • Related Report
      2013 Annual Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Long-term serial cultivation of mouse induced pluripotent stem cells in serum-free and feeder-free defined medium2013

    • Author(s)
      S. Yamasaki, K. Nabeshima, Y. Sotomaru, Y. Taguchi, H. Mukasa, MK. Furue, J. Denry Sato, T. Okamoto,
    • Journal Title

      International Journal of Developmental Biology

      Volume: (印刷中)

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Review Paper : Biomedical advances from tissue culture,2013

    • Author(s)
      T. Okamoto, J. Denry Sato, David W. Barnes, and Gordon H. Sato,
    • Journal Title

      Cytotechnology

      Volume: (印刷中)

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 鎖骨頭蓋異形成症患者歯髄由来細胞を用いた疾患特異的ヒト人工多能性幹細胞(iPS細胞)の樹立2013

    • Author(s)
      向笠英恵、山崎佐知子、田口有紀、嶋本顕、田原栄俊、岡本哲治
    • Journal Title

      日本口腔組織培養学会誌

      Volume: 第22巻 Pages: 15-16

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] インテグリンβ8におけるユビキチンリガーゼhuman double minute 2 (hdm2)結合部位の探索2013

    • Author(s)
      藤井隆彦, 林堂安貴, 坂上泰士, 浜名智昭, 岡本哲治
    • Journal Title

      日本口腔組織培養学会誌

      Volume: 第22巻 Pages: 17-18

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 1α, 25(OH)_2D_3 suppresses HBp17/FGFBP-1 expression via NFκB pathway in oral squamous cell carcinoma :2013

    • Author(s)
      Rosli S. N. Z., 新谷智章、林堂安貴、笛吹恵美子、岡本哲治
    • Journal Title

      日本口腔組織培養学会誌

      Volume: 第22巻 Pages: 19-20

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 1α,25(OH)2D3 down-regulates HBp17/FGFBP-1 expression via NF-κBpathway.2012

    • Author(s)
      Rosli SN, Shintani T, Hayashido Y, Toratani S, Usui E, Okamoto T.
    • Journal Title

      J Steroid Biochem Mol Biol.

      Volume: Oct 24.(12) Pages: 212-219

    • DOI

      10.1016/j.jsbmb.2012.10.011

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Novel Cytotoxic Polyoxygenated Steroids from an Okinawan Sponge <i>Dysidea</i> sp.2012

    • Author(s)
      Govindam SV, Choi BK, Yoshioka Y, Kanamoto A, Fujiwara T, Okamoto T, Ojika M.
    • Journal Title

      Bioscience, Biotechnology, and Biochemistry

      Volume: 76 Issue: 5 Pages: 999-1002

    • DOI

      10.1271/bbb.120017

    • NAID

      10030753103

    • ISSN
      0916-8451, 1347-6947
    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cyclolobatriene, a novel prenylated germacrene diterpene, from the soft coral Lobophytum pauciflorum.2012

    • Author(s)
      Govindam SV, Yoshioka Y, Kanamoto A, Fujiwara T, Okamoto T, Ojika M.
    • Journal Title

      Bioorg Med Chem.

      Volume: 15;20(2) Issue: 2 Pages: 2687-692

    • DOI

      10.1016/j.bmc.2011.12.012

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] Reprogramming efficiencies of hiPS cells with various virus vectors in serum- and feeder-free culture conditions2014

    • Author(s)
      Eri AKAGI, Sachiko YAMASAKI, Atsuko HAMADA, Yuki TAGUCHI, Hanae MUKASA, Manami OHTAKA, Ken NISHIMURA, Mahito NAKANISHI, and Tetsuji OKAMOTO
    • Organizer
      World Congress of Society for In Vitro Biology
    • Place of Presentation
      Hyatt Regency Savannah, Savannah, Georgia, USA
    • Year and Date
      2014-05-30 – 2014-06-04
    • Related Report
      2014 Annual Research Report
  • [Presentation] Generation and maintenance of human induced pluripotent stem cells in serum- and feeder-free culture using Sendai virus vectors2014

    • Author(s)
      HAMADA, Sachiko YAMASAKI, Eri AKAGI, Manami OHTAKA, Ken NISHIMURA, Mahito NAKANISHI, Tetsuji OKAMOTO
    • Organizer
      World Congress of Society for In Vitro Biology
    • Place of Presentation
      Hyatt Regency Savannah, Savannah, Georgia, USA
    • Year and Date
      2014-05-30 – 2014-06-04
    • Related Report
      2014 Annual Research Report
  • [Presentation] センダイウイルスを用いたフィーダー細胞フリー・完全無血清培養系での末梢リンパ球からのhiPS細胞の樹立と維持に関する研究2014

    • Author(s)
      赤木恵理, 山崎佐知子, 岡本哲治、他
    • Organizer
      日本口腔科学会学術集会
    • Place of Presentation
      京王プラザ、東京
    • Year and Date
      2014-05-07 – 2014-05-09
    • Related Report
      2014 Annual Research Report
  • [Presentation] 扁平上皮癌細胞でのオートファジーによる インテグリンαvのプロセシング2014

    • Author(s)
      末松 美玲, 林堂安貴,岡本哲治、他
    • Organizer
      日本口腔科学会学術集会
    • Place of Presentation
      京王プラザ、東京
    • Year and Date
      2014-05-07 – 2014-05-09
    • Related Report
      2014 Annual Research Report
  • [Presentation] センダイウイルスを用いたフィーダーフリー・ 無血清培養系での歯髄細胞由来hiPS細胞の樹立と長期培養2014

    • Author(s)
      濱田充子, 山崎佐知子,岡本哲治、他
    • Organizer
      日本口腔科学会学術集会
    • Place of Presentation
      京王プラザ、東京
    • Year and Date
      2014-05-07 – 2014-05-09
    • Related Report
      2014 Annual Research Report
  • [Presentation] Analysis of binding site of ubiquitin ligase, human double minute 2 in integrin β8 in Oral Squamous Cell Carcinoma cell lines2013

    • Author(s)
      Sakaue T., Hayashido Y., Hamana T., Fujii T. and Okamoto T
    • Organizer
      The 2nd International Symposium Suggestion for the Renaissance from Radiation Disaster
    • Place of Presentation
      Hiroshima
    • Year and Date
      2013-02-11
    • Related Report
      2012 Annual Research Report
  • [Presentation] 1α, 25(OH)_2D_3down-regulates FGF-BP expression through NFκBpathway.2013

    • Author(s)
      Rosli S.N.Z., Shintani T., Hayashido Y., Toratani S., Usui E. and Okamoto T.
    • Organizer
      The 2nd International Symposium Suggestion for the Renaissance from Radiation Disaster
    • Place of Presentation
      Hiroshima
    • Year and Date
      2013-02-11
    • Related Report
      2012 Annual Research Report
  • [Presentation] Generation of disease-specific human induced pluripotent stem (iPS) cells from dental pulp cells of a patient with Cleidocranial dysplasia in serum-and feeder-free culture2013

    • Author(s)
      Mukasa H., Yamasaki S. and Okamoto T.
    • Organizer
      The 2nd International Symposium Suggestion for the Renaissance from Radiation Disaster
    • Place of Presentation
      Hiroshima
    • Year and Date
      2013-02-11
    • Related Report
      2012 Annual Research Report
  • [Presentation] Generation of induced pluripotent stem cells from dental pulp cells in serum-free and feeder-free culture condition2013

    • Author(s)
      Taguchi Y., Yamasaki S., Shimamoto A., Tahara H. and Okamoto T.
    • Organizer
      The 2nd International Symposium Suggestion for the Renaissance from Radiation Disaster
    • Place of Presentation
      Hiroshima
    • Year and Date
      2013-02-11
    • Related Report
      2012 Annual Research Report
  • [Presentation] Participation of heterodimer formation with integrin αv subunit in the stability of integrin β8 subunit in squamous cell carcinoma cells2013

    • Author(s)
      Fujii T., Hayashido Y, Hamana T., Sakaue T. and Okamoto T.
    • Organizer
      The 2nd International Symposium Suggestion for the Renaissance from Radiation Disaster
    • Place of Presentation
      Hiroshima
    • Year and Date
      2013-02-11
    • Related Report
      2012 Annual Research Report
  • [Presentation] Generation of induced pluripotent stem cells from dental pulp cells in serum free and feeder-free culture condition2013

    • Author(s)
      Taguchi Y., Yamasaki S., Shimamoto A., Mukasa H, Tahara H. and Okamoto T.
    • Organizer
      2013 World congress on In Vitro Biology
    • Place of Presentation
      Providence, Rhode Island, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] Down-regulation of HBp17/FGFBP-1 by 1α,25(OH)2D3 inhibits FGF-2 activity in oral squamous cell carcinoma cell line2013

    • Author(s)
      Rosli S.N.Z., Shintani T., Toratani S., Usui E. and Okamoto T.
    • Organizer
      16th Workshop on Vitamin D
    • Place of Presentation
      Sanfrancisco, California, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] Strengthening Research Cooperation in Radiation Nuclear Medicine,2013

    • Author(s)
      Tetsuji Okamoto
    • Organizer
      Technical meeting on research cooperation 2,
    • Place of Presentation
      IAEA, Vienna, Austria
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Radiation, Health, and Society: Post-Fukushima Implications for the Training of Health Professionals2013

    • Author(s)
      Tetsuji Okamoto
    • Organizer
      Technical meeting on research cooperation 1,
    • Place of Presentation
      IAEA, Vienna, Austria
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 1α, 25(OH)_2D_3 down-regulates HBp17/FGFBP-1 by inhibiting NF κ B activity2012

    • Author(s)
      Rosli S. N. Z.、新谷智章、笛吹恵美子、岡本哲治
    • Organizer
      第85回日本生化学会大会
    • Place of Presentation
      福岡
    • Year and Date
      2012-12-15
    • Related Report
      2012 Annual Research Report
  • [Presentation] Analysis of binding site of ubiquitin ligase, human double minute 2 in integrin β82012

    • Author(s)
      坂上泰士、林堂安貴、浜名智昭、藤井隆彦、岡本哲治
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌
    • Year and Date
      2012-09-20
    • Related Report
      2012 Annual Research Report
  • [Presentation] Generation of human induced pluripotent stem (iPS) cells in serum- and feeder-free defined culture from fetal lung fibroblasts and dental pulp2012

    • Author(s)
      Yamasaki S., Shimamoto A., Tahara H. and Okamoto T.
    • Organizer
      World congress on In Vitro Biology
    • Place of Presentation
      Bellevue, Washington, USA
    • Year and Date
      2012-06-25
    • Related Report
      2012 Annual Research Report
  • [Presentation] 1α, 25(OH)_2D_3down-regulates FGF-BP expression through NFκBpathway2012

    • Author(s)
      Rosli S.N.Z., Shintani T., Hayashido Y., Toratani S., Usui E. and Okamoto T.
    • Organizer
      15th Workshop on Vitamin D
    • Place of Presentation
      Houston, Texas, USA
    • Year and Date
      2012-06-21
    • Related Report
      2012 Annual Research Report
  • [Presentation] 鎖骨頭蓋異形成症患者歯髄由来細胞を用いた疾患特異的ヒト人工多能性幹細胞(iPS細胞)の樹立2012

    • Author(s)
      山崎佐知子、嶋本顕、田原栄俊、岡本哲治
    • Organizer
      第66回NPO法人日本口腔科学会学術集会
    • Place of Presentation
      広島
    • Year and Date
      2012-05-17
    • Related Report
      2012 Annual Research Report
  • [Presentation] ヒト人工多能性幹細胞(iPS細胞)の単層無血清培養系の確立2012

    • Author(s)
      田口有紀、山崎佐知子、嶋本顕、田原栄俊、岡本哲治
    • Organizer
      第66回NPO法人日本口腔科学会学術集会
    • Place of Presentation
      広島
    • Year and Date
      2012-05-17
    • Related Report
      2012 Annual Research Report
  • [Presentation] インテグリンβ8におけるユビキチンリガーゼhuman double minute2(hdm2)結合部位の探索2012

    • Author(s)
      藤井隆彦、林堂安貴、浜名智昭、坂上泰士、岡本哲治
    • Organizer
      第66回NPO法人日本口腔科学会学術集会
    • Place of Presentation
      広島
    • Year and Date
      2012-05-17
    • Related Report
      2012 Annual Research Report
  • [Presentation] インテグリンαVサブユニットとの二量体形成がβ8サブユニットの安定化に与える影響2012

    • Author(s)
      坂上泰士、林堂安貴、浜名智昭、藤井隆彦、岡本哲治
    • Organizer
      第66回NPO法人日本口腔科学会学術集会
    • Place of Presentation
      広島
    • Year and Date
      2012-05-17
    • Related Report
      2012 Annual Research Report
  • [Presentation] 口腔扁平上皮癌細胞におけるSP細胞群の癌幹細胞としての細胞・分子生物学的特性の検討2012

    • Author(s)
      伊藤翼、藤井良典、岡本哲治.
    • Organizer
      第66回NPO法人日本口腔科学会学術集会
    • Place of Presentation
      広島
    • Year and Date
      2012-05-17
    • Related Report
      2012 Annual Research Report
  • [Presentation] 口腔扁平上皮癌細胞株を用いた活性型ビタミンD3によるFGFBP/HBp17蛋白発現の検討2012

    • Author(s)
      Rosli S. N. Z.、新谷智章、林堂安貴、笛吹恵美子、岡本哲治
    • Organizer
      第66回NPO法人日本口腔科学会学術集会
    • Place of Presentation
      広島
    • Year and Date
      2012-05-17
    • Related Report
      2012 Annual Research Report
  • [Presentation] 基調講演「口腔がんに対する細胞治療」2012

    • Author(s)
      岡本哲治
    • Organizer
      日中歯科医学大会
    • Place of Presentation
      中国四川省(招待講演)
    • Year and Date
      2012-04-27
    • Related Report
      2012 Annual Research Report
  • [Book] 口腔内科学2014

    • Author(s)
      高戸毅、戸塚、編
    • Total Pages
      500
    • Publisher
      医歯薬出版
    • Related Report
      2013 Annual Research Report

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Published: 2012-04-24   Modified: 2019-07-29  

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