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Function as well as regulation on expression of a novel hyaluronidase in cancer and inflammation

Research Project

Project/Area Number 15K07951
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Biological pharmacy
Research InstitutionMeijo University

Principal Investigator

Yamada Shuhei  名城大学, 薬学部, 教授 (70240017)

Co-Investigator(Renkei-kenkyūsha) MIZUMOTO Shuji  名城大学, 薬学部, 助教 (40443973)
Research Collaborator SUGAHARA Kazuyuki  北海道大学院, 生命科学院, 名誉教授
BASAPPA  バンガロール大学, 助教
YIP George W.C.  シンガポール国立大学, 准教授
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsヒアルロニダーゼ / コンドロイチン硫酸 / ヒアルロン酸 / 癌
Outline of Final Research Achievements

A novel enzyme hyaluronidase-4 (HYAL4) specifically acts on chondroitin sulfate (CS), and may be involved in cancer metastasis. To investigate the role of HYAL4 in metastasis as well as inflammation, several experiments have been performed. HYAL4 gene was stably transfected into a cancer cell line and HYAL4-overexpressing cell lines have been established. HYAL4 shRNA was also stably transfected into a cell line which highly expresses HYAL4, and the knockdown cells have been prepared. The amount of CS in these cell lines has been determined. Influences of the addition of CS oligosaccharides on cell proliferation as well as cell migration of Lewis lung carcinoma cells, have been evaluated. HYAL4-deficient mice have been generated using a CRISPR/CAS9 system. High level expression of HYAL4 in various cancer tissues has been investigated by real-time PCR.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (40 results)

All 2018 2017 2016 2015 Other

All Int'l Joint Research (1 results) Journal Article (9 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 9 results,  Open Access: 6 results,  Acknowledgement Compliant: 3 results) Presentation (26 results) (of which Int'l Joint Research: 4 results,  Invited: 1 results) Book (1 results) Remarks (3 results)

  • [Int'l Joint Research] バンガロール大学(インド)

    • Related Report
      2015 Research-status Report
  • [Journal Article] Defect in dermatan sulfate in urine of patients with Ehlers-Danlos syndrome caused by a CHST14/D4ST1 deficiency2018

    • Author(s)
      Shuji Mizumoto, Tomoki Kosho, Atsushi Hatamochi, Tomoko Honda, Tomomi Yamaguchi, Nobuhiko Okamoto, Noriko Miyake, Shuhei Yamada, and Kazuyuki Sugahara
    • Journal Title

      Clinical Biochemistry

      Volume: 50 Issue: 12 Pages: 670-677

    • DOI

      10.1016/j.clinbiochem.2017.02.018

    • NAID

      120006398760

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Roles of two types of heparan sulfate clusters in Wnt distribution and signaling in Xenopus2018

    • Author(s)
      Yusuke Mii, Takayoshi Yamamoto, Ritsuko Takada, Shuji Mizumoto, Makoto Matsuyama, Shuhei Yamada, Shinji Takada, and Masanori Taira
    • Journal Title

      Nature Communications

      Volume: 8 Issue: 1 Pages: 1973-1973

    • DOI

      10.1038/s41467-017-02076-0

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The reduction of heparan sulphate in the glomerular basement membrane does not augment urinary albumin excretion2018

    • Author(s)
      Satoshi Aoki, Akiko Saito-Hakoda, Takeo Yoshikawa, Kyoko Shimizu, Kiyomi Kisu, Susumu Suzuki, Kiyoshi Takagi, Shuji Mizumoto, Shuhei Yamada, Toin H. van Kuppevelt, Atsushi Yokoyama, Taiji Matsusaka, Hiroshi Sato, Sadayoshi Ito, and Akira Sugawara
    • Journal Title

      Nephrology Dialysis Transplantation

      Volume: 33 Issue: 1 Pages: 26-33

    • DOI

      10.1093/ndt/gfx218

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Vascular abnormalities in the placenta of Chst14-/- fetuses: implications in the pathophysiology of perinatal lethality of the murine model and vascular lesions in human CHST14/D4ST1 deficiency2018

    • Author(s)
      Takahiro Yoshizawa, Shuji Mizumoto, Yuki Takahashi, Shin Shimada, Kazuyuki Sugahara, Jun Nakayama, Shin’ichi Takeda, Yoshihiro Nomura, Yuko Nitahara-Kasahara, Takashi Okada, Kiyoshi Matsumoto, Shuhei Yamada, and Tomoki Kosho
    • Journal Title

      Glycobiology

      Volume: 28 Issue: 2 Pages: 80-89

    • DOI

      10.1093/glycob/cwx099

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of biallelic EXTL3 mutations in a novel type of spondylo-epi-metaphyseal dysplasia2017

    • Author(s)
      *Long Guo, *Nursel H Elcioglu, *Shuji Mizumoto, Zheng Wang, Bilge Noyan, Hatice M Albayrak, Shuhei Yamada, Naomichi Matsumoto, Noriko Miyake, Gen Nishimura, Shiro Ikegawa (equal contribution)
    • Journal Title

      Journal of Human Genetics

      Volume: - Issue: 8 Pages: 797-801

    • DOI

      10.1038/jhg.2017.38

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Chondroitin sulfate N-acetylgalactosaminyltransferase-1 (CSGalNAcT-1) deficiency results in a mild skeletal dysplasia and joint laxity.2017

    • Author(s)
      Julia Vodopiutz, Shuji Mizumoto, Ekkehard Lausch, Antonio Rossi, Sheila Unger, Nikolaus Janocha, Rainer Seidl, Susanne Greber-Platzer, Shuhei Yamada, Thomas Muller, Bernd Jilma, Rudolf Ganger, Andrea Superti-Furga, Shiro Ikegawa, Kazuyuki Sugahara, Andreas R. Janecke.
    • Journal Title

      Human Mutation

      Volume: 38 Issue: 1 Pages: 34-38

    • DOI

      10.1002/humu.23070

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Functional validation of novel compound heterozygous variants in B3GAT3 resulting in severe osteopenia and fractures: expanding the disease phenotype.2016

    • Author(s)
      *Florian Job, *Shuji Mizumoto, Laurie Smith, Natario Couser, Ashley Brazil, Howard Saal, Melanie Patterson, Margaret I. Gibson, Sarah Soden, Neil Miller, Isabelle Thiffault, Carol Saunders, Shuhei Yamada, Katrin Hoffmann, Kazuyuki Sugahara, Emily Farrow. (*equal contribution)
    • Journal Title

      BMC Medical Genetics

      Volume: 17 Issue: 1 Pages: 86-86

    • DOI

      10.1186/s12881-016-0344-9

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Molecular interactions between chondroitin-dermatan sulfate and growth factors/receptors/matrix proteins2016

    • Author(s)
      Shuji Mizumoto, Shuhei Yamada, Kazuyuki Sugahara
    • Journal Title

      Curr. Opin. Struct. Biol.

      Volume: 34 Pages: 35-42

    • DOI

      10.1016/j.sbi.2015.06.004

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Mutations in biosynthetic enzymes for the protein linker region of chondroitin/dermatan/heparan sulfate cause skeletal and skin dysplasias2015

    • Author(s)
      Shuji Mizumoto, Shuhei Yamada, Kazuyuki Sugahara
    • Journal Title

      BioMed Res. Int.

      Volume: 2015 Pages: 861752-861752

    • DOI

      10.1155/2015/861752

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] コンドロイチン硫酸/デルマタン硫酸生合成酵素の先天的欠損による遺伝性疾患2018

    • Author(s)
      山田修平
    • Organizer
      第31回日本軟骨代謝学会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 発達段階の脳におけるコンドロイチン硫酸/ヒアルロン酸分解酵素の発現解析2017

    • Author(s)
      山田修平、三輪一貴、水本秀二
    • Organizer
      第49回日本結合組織学会学術大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 脊髄損傷モデルマウスへのヒアルロニダーゼの投与2017

    • Author(s)
      直井友弥、柴本秀太、水本秀二、勝又優子、森岡 幸、武内恒成、山田修平
    • Organizer
      第63回日本薬学会東海支部総会・大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ヒアルロニダーゼ1および4の基質認識に関与するアミノ酸残基の解析2017

    • Author(s)
      小林智恵里、白水仁子、稲葉史恵、安部優貴子、水本秀二、山田修平
    • Organizer
      第63回日本薬学会東海支部総会・大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] コンドロイチン硫酸を特異的に加水分解するヒアルロニダーゼ4の細胞内局在の解析2017

    • Author(s)
      牧野冴紀、水本秀二、山田修平
    • Organizer
      第36回日本糖質学会年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 発生段階の異なるマウス脳におけるグリコサミノグリカン分解酵素の発現解析2017

    • Author(s)
      禰津瑠里子、三輪一貴、水本秀二、山田修平
    • Organizer
      第36回日本糖質学会年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ヒアルロニダーゼ1および4の基質認識に関与するアミノ酸残基の解析2017

    • Author(s)
      白水仁子、小林智恵里、稲葉史恵、安部優貴子、水本秀二、山田修平
    • Organizer
      第36回日本糖質学会年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] The mammalian chondroitinase, hyaluronidase 4, is produced by human mast cells and generates CS cleavage neo-epitopes2017

    • Author(s)
      Brooke L. Farrugia, Shuji Mizumoto, Megan S. Lord, Shuhei Yamada, Bruce Caterson, John M. Whitelock
    • Organizer
      7 Lakes Proteoglycan Conference
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] マウス脳の各発達過程におけるヒアルロン酸代謝関連酵素の発現の定量的解析2017

    • Author(s)
      山田修平、三輪一貴、水本秀二
    • Organizer
      平成28年度 新学術領域「神経糖鎖生物学」最終シンポジウム
    • Place of Presentation
      名古屋
    • Related Report
      2016 Research-status Report
  • [Presentation] 中枢神経系におけるコンドロイチン硫酸/ヒアルロン酸の分解機構に関する研究2017

    • Author(s)
      永井冴、藤井貴夢、水本秀二、山田修平
    • Organizer
      平成28年度 新学術領域「神経糖鎖生物学」最終シンポジウム
    • Place of Presentation
      名古屋
    • Related Report
      2016 Research-status Report
  • [Presentation] コンドロイチン硫酸に特異的な加水分解酵素であるHYAL4の酵母(Pichia pastoris)での発現および精製2016

    • Author(s)
      柴本秀太、杉田真千子、水本秀二、菅原一幸、山田修平
    • Organizer
      日本薬学会第136年会
    • Place of Presentation
      横浜
    • Year and Date
      2016-03-29
    • Related Report
      2015 Research-status Report
  • [Presentation] 脳・神経系におけるコンドロイチン硫酸/ヒアルロン酸分解機構に関する研究2016

    • Author(s)
      山田修平、永井冴、三輪一貴、水本秀二
    • Organizer
      第48回日本結合組織学会学術大会
    • Place of Presentation
      長崎
    • Related Report
      2016 Research-status Report
  • [Presentation] ヒアルロニダーゼ1および4におけるコンドロイチン硫酸およびヒアルロン酸の認識に関わるアミノ酸残基の解析2016

    • Author(s)
      山田修平、安倍優貴子、山極健太郎、水本秀二
    • Organizer
      第48回日本結合組織学会学術大会
    • Place of Presentation
      長崎
    • Related Report
      2016 Research-status Report
  • [Presentation] コンドロイチン硫酸を特異的に加水分解するヒアルロニダーゼ4の細胞内局在の解析2016

    • Author(s)
      三輪茜音、水本秀二、山田修平
    • Organizer
      第62回日本薬学会東海支部総会 大会
    • Place of Presentation
      名古屋
    • Related Report
      2016 Research-status Report
  • [Presentation] マウス脳におけるコンドロイチン硫酸とヒアルロン酸の分解活性の検出2016

    • Author(s)
      石川輝、水本秀二、山田修平
    • Organizer
      第62回日本薬学会東海支部総会 大会
    • Place of Presentation
      名古屋
    • Related Report
      2016 Research-status Report
  • [Presentation] Quantitative analysis of the expression of hyaluronan-chondroitin sulfate-degrading enzymes in the mouse brain during development.2016

    • Author(s)
      Kazutaka Miwa, Shuji Mizumoto, Shuhei Yamada
    • Organizer
      XXVIII International Carbohydrate Symposium
    • Place of Presentation
      New Orleans, USA
    • Related Report
      2016 Research-status Report
  • [Presentation] Investigation of the amino acid residues in hyaluronidases-1 and -4 responsible for their substrate recognition2016

    • Author(s)
      Yukiko Abe, Kentaro Yamagiwa, Shuji Mizumoto, Shuhei Yamada
    • Organizer
      XXVIII International Carbohydrate Symposium
    • Place of Presentation
      New Orleans, USA
    • Related Report
      2016 Research-status Report
  • [Presentation] Studies on the mechanism of degradation of chondroitin sulfate/hyaluronan in central nervous system2016

    • Author(s)
      Shuhei Yamada, Sae Nagai, Shuji Mizumoto
    • Organizer
      XXVIII International Carbohydrate Symposium
    • Place of Presentation
      New Orleans, USA
    • Related Report
      2016 Research-status Report
  • [Presentation] ヒアルロニダーゼ1および4におけるコンドロイチン硫酸およびヒアルロン酸の認識に関わるアミノ酸残基の解析2015

    • Author(s)
      安倍優貴子、山極健太郎、岩月遥奈、水本秀二、山田修平
    • Organizer
      第38回日本分子生物学会年会・第88回日本生化学会大会合同大会
    • Place of Presentation
      神戸
    • Year and Date
      2015-12-02
    • Related Report
      2015 Research-status Report
  • [Presentation] Investigation of the Amino Acid Residue Responsible for Diferrent Substrate Specificity of Hyaluronidases-1 and -42015

    • Author(s)
      Kentaro Yamagiwa, Haruna Iwatsuki, Yukiko Abe, Shuji Mizumoto, and Shuhei Yamada
    • Organizer
      9th International Conference on Proteoglycans and 10th Pan-Pacific Connective Tissue Societies Symposium
    • Place of Presentation
      Seoul, Korea
    • Year and Date
      2015-08-25
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Quantitative Analysis of the Expression of Hyaluronidases in the Mouse Brain during Development2015

    • Author(s)
      Mayu Mitani, Shuji Mizumoto, Shuhei Yamada
    • Organizer
      9th International Conference on Proteoglycans and 10th Pan-Pacific Connective Tissue Societies Symposium
    • Place of Presentation
      Seoul, Korea
    • Year and Date
      2015-08-25
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Cellular localization of chondroitin sulfate hydrolase, hyaluronidase-42015

    • Author(s)
      Yumiko Nomura, Shuji Mizumoto, and Shuhei Yamada
    • Organizer
      9th International Conference on Proteoglycans and 10th Pan-Pacific Connective Tissue Societies Symposium
    • Place of Presentation
      Seoul, Korea
    • Year and Date
      2015-08-25
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 発生段階の異なるマウス脳におけるヒアルロニダーゼファミリーメンバーの発現解析2015

    • Author(s)
      三谷真夕、水本秀二、山田修平
    • Organizer
      第34回日本糖質学会年会
    • Place of Presentation
      東京
    • Year and Date
      2015-08-02
    • Related Report
      2015 Research-status Report
  • [Presentation] 酵母(Pichia pastoris)を用いたヒアルロニダーゼ4の発現及び精製2015

    • Author(s)
      杉田真千子、柴本秀太、水本秀二、菅原一幸、山田修平
    • Organizer
      第34回日本糖質学会年会
    • Place of Presentation
      東京
    • Year and Date
      2015-08-02
    • Related Report
      2015 Research-status Report
  • [Presentation] ヒアルロニダーゼ1と4の基質認識の違いに関与するアミノ酸残基の解析2015

    • Author(s)
      山極健太郎、岩月遥奈、安倍優貴子、水本秀二、山田修平
    • Organizer
      第34回日本糖質学会年会
    • Place of Presentation
      東京
    • Year and Date
      2015-08-02
    • Related Report
      2015 Research-status Report
  • [Presentation] ヒトの癌細胞株や癌組織におけるヒアルロニダーゼ4の発現解析2015

    • Author(s)
      西島大樹、水本秀二、山田修平
    • Organizer
      第61回日本薬学会東海支部大会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-07-04
    • Related Report
      2015 Research-status Report
  • [Book] Encyclopedia of Polymeric Nanomaterials2015

    • Author(s)
      Kazuyuki Sugahara, Shuji Mizumoto, and Shuhei Yamada
    • Total Pages
      2672
    • Publisher
      Springer
    • Related Report
      2015 Research-status Report
  • [Remarks] 名城大学薬学部病態生化学薬学部病態生化学

    • URL

      http://www-yaku.meijo-u.ac.jp/Research/Laboratory/pathobio/index.html

    • Related Report
      2017 Annual Research Report
  • [Remarks] 名城大学薬学部病態生化学研究室ホームページ

    • URL

      http://www-yaku.meijo-u.ac.jp/Research/Laboratory/pathobio/index.html

    • Related Report
      2016 Research-status Report
  • [Remarks] 名城大学薬学部病態生化学

    • URL

      http://www-yaku.meijo-u.ac.jp/Research/Laboratory/pathobio/index.html

    • Related Report
      2015 Research-status Report

URL: 

Published: 2015-04-16   Modified: 2019-03-29  

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