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Structure and function of glycans expressed on cancer stem cells

Research Project

Project/Area Number 16H05071
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Applied molecular and cellular biology
Research InstitutionNational Institute of Advanced Industrial Science and Technology

Principal Investigator

Tateno Hiroaki  国立研究開発法人産業技術総合研究所, 生命工学領域, 上級主任研究員 (30450670)

Research Collaborator Oda Tatsuya  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2018: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2016: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Keywords糖鎖 / レクチン / 膵がん / 幹細胞 / 癌幹細胞
Outline of Final Research Achievements

In this study, with the aim of developing new therapeutic agents for pancreatic cancer, we performed structural analysis of glycans expressed in pancreatic cancer. As a result, while clarifying the structure of the glycoprotein glycans expressed in pancreatic cancer, a novel glycan marker for pancreatic cancer and a detection probe lectin, rBC2LCN, were identified. We identified glycoprotein ligands of rBC2LCN lectin that is expressed in pancreatic cancer that are expected as new drug target molecules. Furthermore, a lectin-drug conjugate was prepared by fusing rBC2LCN with a drug that was administered around the tumor, in the peritoneal cavity, or in veins of various pancreatic cancer transplantation mouse models. The lectin-drug conjugate was found to show dramatic anti-tumor effects.

Academic Significance and Societal Importance of the Research Achievements

膵がんの5年生存率は未だ10%未満であり、新たな治療薬の開発が切望されている。こうした中、本研究では膵がんの新たな創薬標的となる糖鎖マーカーと、認識するレクチンを同定した。さらに、レクチンに薬剤を融合させたレクチン-薬剤複合体が膵がん移植マウスモデルに対して劇的な抗がん作用を示すことを明らかにした。レクチンはこれまで医薬品として応用されたことのない新たなタンパク質であることから、学術的に大きなインパクトがある。また開発したレクチン-薬剤複合体は未だ有効な治療法がない膵がんの新たな治療戦略として期待され、社会的な意義も大きい。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (45 results)

All 2018 2017 2016 Other

All Int'l Joint Research (1 results) Journal Article (26 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 23 results,  Open Access: 11 results) Presentation (13 results) (of which Int'l Joint Research: 5 results,  Invited: 4 results) Remarks (3 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 2 results)

  • [Int'l Joint Research] The University of California/The Wistar Institute(米国)

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Glycome analysis of extracellular vesicles derived from human induced pluripotent stem cells using lectin microarray2018

    • Author(s)
      Saito Sayoko、Hiemori Keiko、Kiyoi Kayo、Tateno Hiroaki
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 3997-3997

    • DOI

      10.1038/s41598-018-22450-2

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The trimeric solution structure and fucose-binding mechanism of the core fucosylation-specific lectin PhoSL2018

    • Author(s)
      Yamasaki Kazuhiko、Yamasaki Tomoko、Tateno Hiroaki
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 7740-7740

    • DOI

      10.1038/s41598-018-25630-2

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification, Characterization, and X-ray Crystallographic Analysis of a Novel Type of Lectin AJLec from the Sea Anemone Anthopleura japonica2018

    • Author(s)
      Unno Hideaki、Nakamura Azusa、Mori Shingo、Goda Shuichiro、Yamaguchi Kenichi、Hiemori Keiko、Tateno Hiroaki、Hatakeyama Tomomitsu
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 11516-11516

    • DOI

      10.1038/s41598-018-29498-0

    • NAID

      120006987968

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Reduced fucosylation in the distal intestinal epithelium of mice subjected to chronic social defeat stress2018

    • Author(s)
      Omata Yasuhiro、Aoki Reiji、Aoki-Yoshida Ayako、Hiemori Keiko、Toyoda Atsushi、Tateno Hiroaki、Suzuki Chise、Takayama Yoshiharu
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 13199-13199

    • DOI

      10.1038/s41598-018-31403-8

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Fucose-specific lectin of Aspergillus fumigatus: binding properties and effects on immune response stimulation2018

    • Author(s)
      Sakai Kanae、Hiemori Keiko、Tateno Hiroaki、Hirabayashi Jun、Gonoi Tohru
    • Journal Title

      Medical Mycology

      Volume: 57 Issue: 1 Pages: 71-83

    • DOI

      10.1093/mmy/myx163

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Evaluation of the quality of antibody drugs and cell therapy products using lectin microarray2018

    • Author(s)
      Tateno Hiroaki
    • Journal Title

      Electrophoresis Letters

      Volume: 62 Issue: 1 Pages: 27-30

    • DOI

      10.2198/electroph.62.27

    • NAID

      130007393790

    • ISSN
      2189-2628, 2189-2636
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Development of a Sensitive Microarray Platform for the Ranking of Galectin Inhibitors: Identification of a Selective Galectin-3 Inhibitor2017

    • Author(s)
      Dion Johann、Advedissian Tamara、Storozhylova Nataliya、Dahbi Samir、Lambert Annie、Deshayes Fr?d?rique、Viguier Mireille、Tellier Charles、Poirier Fran?oise、T?letch?a St?phane、Dussouy Christophe、Tateno Hiroaki、Hirabayashi Jun、Grandjean Cyrille
    • Journal Title

      ChemBioChem

      Volume: 18 Issue: 24 Pages: 2428-2440

    • DOI

      10.1002/cbic.201700544

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Distinct roles for each N-glycan branch interacting with mannose-binding type Jacalin-related lectins Orysata and Calsepa.2017

    • Author(s)
      Nagae M, Mishra SK, Hanashima S, Tateno H, Yamaguchi Y
    • Journal Title

      Glycobiology

      Volume: 27(12) Issue: 12 Pages: 1120-1133

    • DOI

      10.1093/glycob/cwx081

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A novel therapeutic strategy for pancreatic cancer: Targeting cell surface glycan using rBC2LC-N lectin-drug conjugate (LDC)2017

    • Author(s)
      Shimomura Osamu、Oda Tatsuya、Tateno Hiroaki、Ozawa Yusuke、Kimura Sota、Sakashita Shingo、Noguchi Masayuki、Hirabayashi Jun、Asashima Makoto、Ohkohchi Nobuhiro
    • Journal Title

      Molecular Cancer Therapeutics

      Volume: 17 Issue: 1 Pages: 183

    • DOI

      10.1158/1535-7163.mct-17-0232

    • URL

      https://pure.teikyo.jp/en/publications/ec41d645-0da9-47cb-bc5b-87fe02d806c0

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Engineering of a Potent Recombinant Lectin-Toxin Fusion Protein to Eliminate Human Pluripotent Stem Cells2017

    • Author(s)
      Tateno Hiroaki、Minoshima Fumi、Saito Sayoko
    • Journal Title

      Molecules

      Volume: 22 Issue: 7 Pages: 1151-1151

    • DOI

      10.3390/molecules22071151

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Lectin microarray analysis of isolated polysaccharides from Sasa veitchii2017

    • Author(s)
      Yagi Hirokazu、Tateno Hiroaki、Hayashi Kyoko、Hayashi Toshimitsu、Takahashi Katsuhiko、Hirabayashi Jun、Kato Koichi、Tsuboi Masamichi
    • Journal Title

      Biosci. Biotechnol. Biochem.

      Volume: 81 Issue: 9 Pages: 1687-1689

    • DOI

      10.1080/09168451.2017.1340089

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sugar-Binding Profiles of Chitin-Binding Lectins from the Hevein Family: A Comprehensive Study2017

    • Author(s)
      Itakura Yoko、Nakamura-Tsuruta Sachiko、Kominami Junko、Tateno Hiroaki、Hirabayashi Jun
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 18 Issue: 6 Pages: 1160-1160

    • DOI

      10.3390/ijms18061160

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Engineering of recombinant Wisteria floribunda agglutinin specifically binding to GalNAcβ1,4GlcNAc (LacdiNAc)2017

    • Author(s)
      Sato Takashi、Tateno Hiroaki、Kaji Hiroyuki、Chiba Yasunori、Kubota Tomomi、Hirabayashi Jun、Narimatsu Hisashi
    • Journal Title

      Glycobiology

      Volume: 27 Issue: 8 Pages: 743-754

    • DOI

      10.1093/glycob/cwx038

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Isolation of Rice Bran Lectins and Characterization of Their Unique Behavior in Caco-2 Cells2017

    • Author(s)
      Nakata Hajime、Lin Ching、Abolhassani Maryam、Ogawa Tomohisa、Tateno Hiroaki、Hirabayashi Jun、Muramoto Koji
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 18 Issue: 5 Pages: 1052-1052

    • DOI

      10.3390/ijms18051052

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Carbohydrate recognition by the rhamnose-binding lectin SUL-I with a novel three-domain structure isolated from the venom of globiferous pedicellariae of the flower sea urchin Toxopneustes pileolus2017

    • Author(s)
      Hatakeyama Tomomitsu、Ichise Ayaka、Unno Hideaki、Goda Shuichiro、Oda Tatsuya、Tateno Hiroaki、Hirabayashi Jun、Sakai Hitomi、Nakagawa Hideyuki
    • Journal Title

      Protein Science

      Volume: 26 Issue: 8 Pages: 1574-1583

    • DOI

      10.1002/pro.3185

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of a practical sandwich assay to detect human pluripotent stem cells using cell culture media2017

    • Author(s)
      Tateno H, Hiemori K, Hirayasu K, Sougawa N, Fukuda M, Warashina M, Amano M, Funakoshi T, Sadamura Y, Miyagawa S, Saito A, Sawa Y, Shofuda T, Sumida M, Kanemura Y, Nakamura M, Okano H, Onuma Y, Ito Y, Asashima M, Hirabayash J.
    • Journal Title

      Regenerative Therapy

      Volume: 6 Pages: 1

    • DOI

      10.1016/j.reth.2016.12.002

    • URL

      https://pure.teikyo.jp/en/publications/a15dcde1-adbd-49b5-8eb3-dc03194d8936

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] レクチンを用いたヒト間葉系幹細胞の品質評価2017

    • Author(s)
      舘野浩章
    • Journal Title

      B&I

      Volume: 75 Pages: 134-136

    • NAID

      40021142220

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Stem cell glycomics: Structure, function, and application2016

    • Author(s)
      舘野浩章
    • Journal Title

      生化学

      Volume: 88 Issue: 6 Pages: 761-765

    • DOI

      10.14952/SEIKAGAKU.2016.880761

    • NAID

      40021054375

    • ISSN
      0037-1017
    • Year and Date
      2016-12-25
    • Related Report
      2016 Annual Research Report
  • [Journal Article] Affinity-based Glycan Analysis2016

    • Author(s)
      Tateno H
    • Journal Title

      Proteomics

      Volume: 16 Issue: 24 Pages: 3055-3055

    • DOI

      10.1002/pmic.201670314

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Carbohydrate-binding domain of the POMGnT1 stem region modulates O-mannosylation sites of α-dystroglycan.2016

    • Author(s)
      Kuwabara N, Manya H, Yamada T, Tateno H, Kanagawa M, Kobayashi K, Akasaka-Manya K, Hirose Y, Mizuno M, Ikeguchi M, Toda T, Hirabayashi J, Senda T, Endo T, Kato R.
    • Journal Title

      Proc Natl Acad Sci U S A.

      Volume: 113 Issue: 33 Pages: 9280-9285

    • DOI

      10.1073/pnas.1525545113

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification, Characterization, and X-ray Crystallographic Analysis of a Novel Type of Mannose-Specific Lectin CGL1 from the Pacific Oyster Crassostrea gigas2016

    • Author(s)
      Unno H, Matsuyama K, Tsuji Y, Goda S, Hiemori K, Tateno H, Hirabayashi J, Hatakeyama T.
    • Journal Title

      Sci Rep

      Volume: 6 Issue: 1 Pages: 29135-29135

    • DOI

      10.1038/srep29135

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A rationally engineered yeast pyruvyltransferase Pvg1p introduces sialylation-like properties in neo-human-type complex oligosaccharide.2016

    • Author(s)
      Higuchi Y, Yoshinaga S, Yoritsune K, Tateno H, Hirabayashi J, Nakakita S, Kanekiyo M, Kakuta Y, Takegawa K.
    • Journal Title

      Sci Rep

      Volume: 6 Issue: 1 Pages: 26349-26349

    • DOI

      10.1038/srep26349

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of the cysteine residue responsible for oxidative inactivation of mouse galectin-22016

    • Author(s)
      Tamura M, Sasai A, Ozawa R, Saito M, Yamamoto K, Takeuchi T, Ohtake K, Tateno H, Hirabayashi J, Kobayashi J, Arata Y
    • Journal Title

      J Biochem

      Volume: 160 Issue: 4 Pages: 233-241

    • DOI

      10.1093/jb/mvw029

    • NAID

      120006239298

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cell surface localization of importin α1/KPNA2 affects cancer cell proliferation by regulating FGF1 signalling.2016

    • Author(s)
      Yamada K., Miyamoto Y., Tsujii A., Moriyama T., Ikuno Y., Shiromizu T., Serada S., Fujimoto M., Tomonaga T., Naka T., Oka M.
    • Journal Title

      Sci Rep

      Volume: 6 Issue: 1 Pages: 24823-24823

    • DOI

      10.1038/srep24823

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] α2-6sialylation is a marker of the differentiation potential of human mesenchymal stem cells2016

    • Author(s)
      Tateno H, Saito S, Hiemori K, Kiyoi K, Hasehira K, Toyoda M, Onuma Y, Ito Y, Akutsu H, Hirabayashi J
    • Journal Title

      Glycobiology

      Volume: 26 Pages: 1328-1337

    • DOI

      10.1093/glycob/cww039

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Two carbohydrate recognizing domains from Cycas revoluta leaf lectin show the distinct sugar-binding specificity-A unique mannooligosaccharide recognition by N-terminal domain2016

    • Author(s)
      Shimokawa M, Haraguchi T, Minami Y, Yagi F, Hiemori K, Tateno H, Hirabayashi J
    • Journal Title

      J Biochem

      Volume: 160 Issue: 1 Pages: 27-35

    • DOI

      10.1093/jb/mvw011

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Presentation] レクチンマイクロアレイによる エクソソームのグライコーム解析2018

    • Author(s)
      舘野浩章
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Glycome of stem cells and application to regenerative medicine2018

    • Author(s)
      舘野浩章
    • Organizer
      JAACT2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Glycome of stem cells: functional insight and social implementation2018

    • Author(s)
      舘野浩章
    • Organizer
      10th ACGG conference
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] ヒトiPS細胞由来エクソソームのグライコーム解析2018

    • Author(s)
      齊藤佐代子、箕嶋文、比江森恵子、 丹羽祐貴、舘野浩章
    • Organizer
      第37回日本糖質学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 糖鎖を標的としたヒト間葉系幹細胞品質管理技術の開発2017

    • Author(s)
      舘野浩章
    • Organizer
      第16回日本再生医療学会総会
    • Place of Presentation
      仙台国際センター
    • Year and Date
      2017-03-08
    • Related Report
      2016 Annual Research Report
  • [Presentation] 造腫瘍性を有するヒトES/iPS細胞の除去と非侵襲的モニタリング技術2017

    • Author(s)
      舘野浩章
    • Organizer
      第16回日本再生医療学会総会
    • Place of Presentation
      仙台国際センター
    • Year and Date
      2017-03-07
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] レクチンを用いた幹細胞ターゲティング技術の開発と応用2017

    • Author(s)
      舘野浩章
    • Organizer
      2017年度生命科学系学会合同年次大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Glycome of Stem Cells and Application to Regenerative Medicine2017

    • Author(s)
      Hiroaki Tateno
    • Organizer
      24th International Symposium on Glycoconjugates (Glyco24)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] レクチン工学によるヒトES/iPS細胞検出除去技術の開発と再生医療への応用2017

    • Author(s)
      舘野浩章
    • Organizer
      第36回日本糖質学会年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] レクチンマイクロアレイを用いたバイオ・細胞医薬品評価技術の開発2017

    • Author(s)
      舘野浩章
    • Organizer
      第67回日本電気泳動学会シンポジウム
    • Related Report
      2017 Annual Research Report
  • [Presentation] a2-6シアリルN型糖鎖はヒト間葉系幹細胞の分化ポテンシャルマーカーである2016

    • Author(s)
      舘野浩章、馳平加代、平林淳
    • Organizer
      第35回日本糖質学会年会
    • Place of Presentation
      高知市文化プラザかるぽーと
    • Year and Date
      2016-09-02
    • Related Report
      2016 Annual Research Report
  • [Presentation] GLYCAN-TARGETED ELIMINATION OF TUMORIGENIC HUMAN PLURIPOTENT STEM CELLS BY AN ENGINEERED LECTIN-TOXIN FUSION PROTEIN DRUG2016

    • Author(s)
      Hiroaki Tateno, Yasuko Onuma, Yuzuru Ito, Jun Hirabayashi
    • Organizer
      ISSCR2016
    • Place of Presentation
      Moscone West
    • Year and Date
      2016-06-22
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] a2-6SIALYLATION IS A MARKER OF THE DIFFERENTIATION POTENTIAL OF HUMAN MESENCHYMAL STEM CELLS2016

    • Author(s)
      Hiroaki Tateno, Masashi Toyoda, Yasuko Onuma, Yuzuru Ito, Hidenori Akutsu, Jun Hirabayashi
    • Organizer
      ISSCR2016
    • Place of Presentation
      Moscone West
    • Year and Date
      2016-06-22
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Remarks] 産業技術総合研究所創薬基盤研究部門

    • URL

      https://unit.aist.go.jp/brd/jp/groups/cgtrg/cgtrg.html

    • Related Report
      2018 Annual Research Report
  • [Remarks] 膵がん細胞表面の糖鎖をレクチン融合薬で狙い撃ち

    • URL

      http://www.aist.go.jp/aist_j/press_release/pr2017/pr20170926/pr20170926.html

    • Related Report
      2017 Annual Research Report
  • [Remarks] 国立研究開発法人産業技術総合研究所創薬基盤研究部門細胞グライコーム標的技術グループ

    • URL

      https://unit.aist.go.jp/brd/jp/groups/cgtrg/cgtrg.html

    • Related Report
      2016 Annual Research Report
  • [Patent(Industrial Property Rights)] がん細胞の検出方法、がん細胞内に物質を導入するための試薬、及びがん治療用組成物2017

    • Inventor(s)
      舘野 浩章他7名
    • Industrial Property Rights Holder
      舘野 浩章他7名
    • Industrial Property Rights Type
      特許
    • Filing Date
      2017
    • Related Report
      2017 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] がんの診断及び治療方法2016

    • Inventor(s)
      舘野浩章、他7名
    • Industrial Property Rights Holder
      舘野浩章、他7名
    • Industrial Property Rights Type
      特許
    • Filing Date
      2016-10-05
    • Related Report
      2016 Annual Research Report
    • Overseas

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Published: 2016-04-21   Modified: 2020-03-30  

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