Immune evasion mechanisms from NK immunity by cancer cell-surface O-glycans

• Project/Area Number: 22570131
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Hirosaki University
• Principal Investigator: TSUBOI Shigeru 弘前大学, 医学(系)研究科(研究院), 研究員 (20526727)
• Co-Investigator(Kenkyū-buntansha): 大山 力 弘前大学, 大学院医学研究科, 教授 (80282135)
• Co-Investigator(Renkei-kenkyūsha): 西村 紳一郎 北海道大学, 大学院理学研究科, 教授 (00183898)
• Project Period (FY): 2010-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2013: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 癌転移 / 腫瘍免疫 / NK細胞 / 糖鎖生物学 / 免疫 / 膀胱がん / 前立腺がん / 膀胱癌 / ＮＫ細胞 / 前立腺癌

Research Abstract

Most cancer cells are rejected by host tumor immunosurveillance systems. NK cells are the major effector lymphocytes in tumor rejection responses. However, malignat cancer cells take various strategies to evade tumor rejection systems by NK cells. Those cancer cells survive longer in host, resulting in the promotion of metastasis. We have identified a new immune evasion strategy by cancer cells. Some cancer cells use a certain type of cell-surface carbohydrates to evade NK cell attack, thereby increasing the chance to metastasize.In addition, we discovered a novel cell biological mechanism underlying the extravasation of metastatic cancer cells from blood vessels of the metastasis target organ.

Research Products

• [Journal Article] Vimentin intermediate filament and plectin provide a scaffold for invadopodia, facilitating cancer cell invasion and extravasation for metastasis (2014)
  • Author(s): Sutoh Yoneyama, M., Hatakeyama, S.,Habuchi, T., Inoue, T., Nakamura, T.,Funyu, T., Wiche, G., Ohyama, C. and Tsuboi, S.
  • Journal Title: European Journal of Cell Biology Volume: (in press) Issue: 4 Pages: 157-169
  • DOI: 10.1016/j.ejcb.2014.03.002
  • Peer Reviewed
• [Journal Article] Invadopodia play an essential role in transendothelial invasion during muscle invasion of bladder cancer cells (2014)
  • Author(s): Imanishi, K., Sutoh Yoneyama, M.,Hatakeyama, S., Yamamoto, H., Koie, T.,Saitoh, H., Yamaya, K., Funyu, T.,Nakamura, T., Ohyama, C. and Tsuboi,S.
  • Journal Title: Molecular Medicine Reports Volume: (in press) Issue: 6 Pages: 2159-2165
  • DOI: 10.3892/mmr.2014.2113
  • Peer Reviewed
• [Journal Article] Extravasation during bladder cancer metastasis requires cortactin-mediated invadopodia formation (2014)
  • Author(s): Tokui, N., Sutoh Yoneyama, M.,Hatakeyama, S., Yamamoto, H., Koie, T.,Saitoh, H., Yamaya, K., Funyu, T.,Nakamura, T., Ohyama, C. and Tsuboi,S.
  • Journal Title: Molecular Medicine Reports Volume: 9 Issue: 4 Pages: 1142-1146
  • DOI: 10.3892/mmr.2014.1965
  • Peer Reviewed
• [Journal Article] Vimentin intermediate filament and plectin provide a scaffold for invadopodia, facilitating cancer cell invasion and extravasation for metastasis. (2014)
  • Author(s): Sutoh Yoneyama, M., Hatakeyama, S., Habuchi, T., Inoue, T., Nakamura, T., Funyu, T., Wiche, G., Ohyama, C. and *Tsuboi, S.
  • Journal Title: European Journal of Cell Biology Volume: in press
  • Peer Reviewed
• [Journal Article] In vivo selection of high-metastatic subline of bladder cancer cell and itscharacterization (2013)
  • Author(s): Sugiyama, N., Sutoh Yoneyama, M.,Hatakeyama, S., Yamamoto, H.,Okamoto, A., Koie, T., Saitoh, H.,Yamaya, K., Funyu, T., Nakamura, T.,Ohyama, C. and Tsuboi, S.
  • Journal Title: Oncology Research Volume: 20 Issue: 7 Pages: 289-295
  • DOI: 10.3727/096504013x13639794277644
  • Peer Reviewed
• [Journal Article] Core2 O-glycan-expressing prostate cancer cells are resistant to NK cell immunity (2013)
  • Author(s): Okamoto, T., Sutoh Yoneyama, M.,Hatakeyama, S., Mori, K., Yamamoto, H.,Koie, T., Saitoh, H., Yamaya, K., Funyu,T., Fukuda, M., Ohyama, C. and Tsuboi,S.
  • Journal Title: Molecular Medicine Reports Volume: 7 Issue: 2 Pages: 359-364
  • DOI: 10.3892/mmr.2012.1189
  • Peer Reviewed
• [Journal Article] O-グリカンによる膀胱癌の新規免疫逃避機構 (2013)
  • Author(s): 坪井 滋、 畠山真吾、 大山 力
  • Journal Title: 病理と臨床 Volume: 31(8) Pages: 868-874
• [Journal Article] Immunosuppressive Functions of Core2 <i>O</i>-Glycans against NK Immunity (2013)
  • Author(s): Tsuboi, S.
  • Journal Title: Trends in Glycoscience and Glycotechnology Volume: 25 Issue: 143 Pages: 117-123
  • DOI: 10.4052/tigg.25.117
  • NAID: 10031190627
  • ISSN: 0915-7352, 1883-2113
  • Peer Reviewed
• [Journal Article] Ｏ-グリカンによる膀胱癌の新規免疫逃避機構 (2013)
  • Author(s): 坪井 滋、畠山真吾、大山 力
  • Journal Title: 病理と臨床 Volume: 13 Pages: 868-874
  • Peer Reviewed
• [Journal Article] Misfolded Glycoproteins as Probes for Analysis of Folding Sensor Enzyme UDP-Glucose (2013)
  • Author(s): Tsuboi, S.
  • Journal Title: Trends in Glycoscience and Glycotechnology Volume: 25 Issue: 141 Pages: 1-12
  • DOI: 10.4052/tigg.25.1
  • NAID: 130004841363
  • ISSN: 0915-7352, 1883-2113
  • Peer Reviewed
• [Journal Article] MUC1 carrying core 2 O-glycans functions as a molecular shield against NK cell attack, promoting bladder tumor metastasis (2012)
  • Author(s): Suzuki Y, et al.
  • Journal Title: International Journal of Onocology Volume: (未定)(in press) Pages: 1831-1838
  • DOI: 10.3892/ijo.2012.1411
  • Peer Reviewed
• [Journal Article] Tumor Defense Systems Using <i>O</i>-Glycans (2012)
  • Author(s): Tsuboi, S.
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 35 Issue: 10 Pages: 1633-1636
  • DOI: 10.1248/bpb.b12-00367
  • NAID: 130001872366
  • ISSN: 0918-6158, 1347-5215
  • Peer Reviewed
• [Journal Article] Two opposing roles of O-glycans in tumor metastasis (2012)
  • Author(s): Tsuboi, S., Hatakeyama, S., Ohyama,C. and Fukuda, M.
  • Journal Title: Trends in Molecular Medicine Volume: 18 Issue: 4 Pages: 224-232
  • DOI: 10.1016/j.molmed.2012.02.001
  • Peer Reviewed
• [Journal Article] A novel strategy for evasion of NK cell immunity by tumours expressing core2 O-glycans (2011)
  • Author(s): 坪井滋、盛和行, 他
  • Journal Title: EMBO J Volume: 30(15) Issue: 15 Pages: 3173-3185
  • DOI: 10.1038/emboj.2011.215
  • Peer Reviewed
• [Journal Article] Requirement for FBP17 in invadopodia formation by invasive bladder tumor cells (2011)
  • Author(s): Yamamoto, H., Sutoh, M., Hatakeyama,S., Hashimoto, Y.,Yoneyama, T., Koie, T.,Saitoh, H., Yamaya, K., Funyu, T.,Nakamura, T., Ohyama, C. and Tsuboi,S.
  • Journal Title: Journal of Urology Volume: 185 Issue: 5 Pages: 1930-1938
  • DOI: 10.1016/j.juro.2010.12.027
  • Peer Reviewed
• [Journal Article] Invadopodia formation by bladder tumor cells (2010)
  • Author(s): Sutoh, M., Hashimoto, Y.,Yoneyama, T.,Yamamoto, H., Hatakeyama, S., Koie, T.,Okamoto, A., Yamaya, K., Saitoh, H.,Funyu, T., Nakamura, T., Sato, T.,Ohyama, C. and Tsuboi, S.
  • Journal Title: Oncology Research Volume: 19 Issue: 2 Pages: 85-92
  • DOI: 10.3727/096504010x12875107808008
  • Peer Reviewed
• [Presentation] Core2 O-glycan-expressing prostate cancer cells are resistant to NK cell immunity. (2014)
  • Author(s): 岡本 哲平
  • Organizer: 第１０回臨床糖鎖研究会
  • Place of Presentation: 青森県弘前市
• [Presentation] 膀胱癌細胞の血管外脱出過程の解析 (2014)
  • Author(s): 坪井 滋
  • Organizer: 第１５１回弘前医学会例会
  • Place of Presentation: 青森県弘前市
• [Presentation] Vimentin intermediate filament and plectin provide a scaffold for invadopodiam, facilitating cancer cell invasion (2013)
  • Author(s): Tsuboi, S.
  • Organizer: Invadosome 2013 Cell Migration and Invasion inPhysiology and Pathology
  • Place of Presentation: Radboud University Medical Center, Nijmegen, The Netherlands
  • Year and Date: 2013-10-15
• [Presentation] Vimentin intermediate filament and plectin provide a scaffold for invadopodia, facilitating cancer cell invasion (2013)
  • Author(s): Tsuboi, S.
  • Organizer: Invadosome 2013
  • Place of Presentation: Nijmegen, The Netherlands
• [Presentation] 糖鎖による癌の免疫逃避機構 (2013)
  • Author(s): 坪井 滋
  • Organizer: 第３２回日本糖質学会
  • Place of Presentation: 大阪市
  • Invited
• [Presentation] Plectin 1 anchoring invadopodia to vimentin intermediate filament is a critical molecular step for cancer cell extaravasation and metastasis (2013)
  • Author(s): 坪井 滋
  • Organizer: 第６５回日本細胞生物学会大会
  • Place of Presentation: 名古屋市
• [Presentation] 糖鎖を利用した癌細胞自己防御システム (2012)
  • Author(s): 坪井 滋
  • Organizer: 東北薬科大学分子生体膜研究所戦略的研究基盤形成支援事業シンポジウム
  • Place of Presentation: 東北薬科大学 仙台
  • Year and Date: 2012-11-03
• [Presentation] 細胞表面のO-glycanを利用した癌細胞の新しい免疫逃避機構 (2011)
  • Author(s): 坪井滋
  • Organizer: 第77回生化学会東北支部会
  • Place of Presentation: 仙台(東北大学)
  • Year and Date: 2011-07-23
• [Presentation] 細胞表面のO-glycanを利用した癌細胞の新しい免疫逃避機構 (2010)
  • Author(s): 坪井滋
  • Organizer: 第83回日本生化学会大会
  • Place of Presentation: 神戸(神戸ポートアイランド)
  • Year and Date: 2010-12-10
• [Presentation] O-グリカンによる癌の免疫逃避機構
  • Author(s): 坪井 滋
  • Organizer: 第６回東北糖鎖研究会
  • Place of Presentation: 弘前（弘前大学）
• [Presentation] 糖鎖を利用した癌細胞自己防御システム
  • Author(s): 坪井 滋
  • Organizer: 東北薬科大学分子生体膜研究所 戦略的研究基盤形成支援事業シンポジウム
  • Place of Presentation: 仙台（東北薬科大学）
  • Invited
• [Book] Handbook of Glycosyltransferases and Related Genes Beta-1,3-galactosyl-O-glycosyl-gly Coprotein beta-1,6-N-acetylglucosaminyltras nsferase 1 (GCNT1) (C2GnT-L) and Beta-1,3-galactosyl-O-glycosyl-gly coprotein beta-1,6-N-acetylglucosaminyltras nsferase 3 (GCNT4) (C2GnT-T) (2014)
  • Author(s): Shigeru Tsuboi(分担執筆)(Eds. by Naoyuki Taniguchi, Koichi Honke, Minoru Fukuda, Hisashi Narimatsu, Yoshiki Yamaguchi and Takashi Angata)
  • Publisher: Springer
  • URL: http://www.springerreference.com/docs/html/chapterdbid/332082.html
• [Book] Handbook of Glycosyltransferases and Related Genes (2014)
  • Author(s): Tsuboi, S. and Fukuda, M.
  • Total Pages: 5
  • Publisher: Springer
• [Patent(Industrial Property Rights)] 特許権 (2010)
  • Inventor(s): 大山 力、坪井 滋
  • Industrial Property Rights Holder: 弘前大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2010-182641
  • Filing Date: 2010-08-17
  • Overseas
• [Patent(Industrial Property Rights)] 特許権 (2010)
  • Inventor(s): 大山力, 坪井滋
  • Industrial Property Rights Holder: 弘前大学
  • Industrial Property Number: 2010-182641
  • Filing Date: 2010-08-17
  • Acquisition Date: 2010