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

2013 Fiscal Year Final Research Report

• 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
• Keywords: 癌転移 / 腫瘍免疫 / NK細胞 / 糖鎖生物学

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)
  • 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)
  • 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 Pages: 1142-1146
  • DOI: 10.3892/mmr.2014.1965
  • 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 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 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 O-glycans against NK immunity (2013)
  • Author(s): Tsuboi, S.
  • Journal Title: Trends in Glycoscience and Glycotechnology Volume: 25(143) Pages: 117-123
  • DOI: 10.4052/tigg.25.117
  • 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): Suzukuki, Y., Sutoh, M., Hatakeyama, S.,Mori, K., Yamamoto, H., Koie, T., Saitoh,H., Yamaya, K., Funyu, T., Habuchi, T.,Arai, Y., Fukuda, M., Ohyama, C. and Tsuboi, S.
  • Journal Title: International Journal of Oncology Volume: 40 Pages: 1831-1838
  • DOI: 10.3892/ijo.2012.1411
  • Peer Reviewed
• [Journal Article] Tumor defense systems using O-glycans (2012)
  • Author(s): Tsuboi, S.
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 35(10) Pages: 1633-1636
  • DOI: 10.1248/bpb.b12-00367
  • 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 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): Tsuboi, S., Sutoh, M., Hatakeyama, S.,Hiraoka, N., Habuchi, T., Horikawa, Y.,Hashimoto, Y.,Yoneyama, T., Mori, K.,Koie, T., Nakamura, T., Saitoh, H.,Yamaya, K., Funyu, T., Fukuda, M. and Ohyama, C.
  • Journal Title: EMBO Journal Volume: 30 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 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 Pages: 85-92
  • DOI: 10.3727/096504010X12875107808008
  • Peer Reviewed
• [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] 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
• [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
• [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: 特許権
  • Industrial Property Number: 特願2010-182641
  • Filing Date: 2010-08-17
  • Overseas