腫瘍ムチンとしてのエピグリカニン／Ｍｕｃ２１の免疫抑制能の解析

2013 年度 研究成果報告書

• 研究課題/領域番号: 21390018
• 研究種目: 基盤研究(B)
• 配分区分: 補助金
• 応募区分: 一般
• 研究分野: 生物系薬学
• 研究機関: 東京大学
• 研究代表者: 入村 達郎 東京大学, 薬学研究科(研究院), 名誉教授 (80092146)
• 研究期間 (年度): 2009-04-01 – 2013-03-31
• キーワード: ムチン / 免疫抑制 / がん / エピグリカニン / アポトーシス

研究概要

マウス／ヒトエピグリカニンMUC21を強制発現させた細胞の生物学的及び免疫学的な挙動を解析し、グリコフォームの影響を精査した。マウスMuc21を発現した細胞は、培養容器や細胞外マトリックス分子に対する接着性が低く、Muc21 が細胞表面のインテグリンの機能を低下させたことが示唆された。トランスフェクタントは細胞傷害性に対する感受性が低く、このムチンを発現する細胞が免疫監視を逃れる機構を説明する。アポトーシス耐性などの性質はヒトMUC21のトランスフェクタントでもみられた。

研究成果

• [雑誌論文] Heparanase-mediated cleavage of macromolecular heparin accelerates release of granular components of mast cells from extracellular matrices (2013)
  • 著者名/発表者名: Higashi N, Waki M, Sue M, Kogane Y, Shida H, Tsunekawa N, Hasan A, Sato T, Kitahara A, Kasaoka T, Hayakawa Y, Nakajima M, Irimura T
  • 雑誌名: Biochem J 巻: (published online)
• [雑誌論文] A unique dermal dendritic cell subset that skews the immune response toward Th2 (2013)
  • 著者名/発表者名: Murakami R, Denda-Nagai K, Hashimoto S, Nagai S, Hattori M, Irimura T
  • 雑誌名: PLoS One 巻: 8(9) ページ: e73270
• [雑誌論文] Chemokine CXCL16 suppresses liver metastasis of colorectal cancer via augmentation of tumor-infiltrating natural killer T cells in a murine model (2013)
  • 著者名/発表者名: Kee JY, Ito A, Hojo S, Hashimoto I, Igarashi Y, Tsukada K, Irimura, T, Shibahara N, Nakayama T, Yoshie O, Sakurai H, Saiki I, Koizumi K
  • 雑誌名: Oncol Rep 巻: 29 ページ: 975-982
• [雑誌論文] Functional roles of TRAIL-DR5 interaction in B16F10 by activating NFκB pathway to induce metastatic potential (2013)
  • 著者名/発表者名: Takahashi K, Takeda K, Saiki I, Irimura T, Hayakawa Y
  • 雑誌名: Cancer Sci 巻: 104(5) ページ: 558-562
• [雑誌論文] Enhancement of in vitro cell motility and invasiveness of human malignant pleural mesothelioma cells through the HIF-1alpha–MUC1 pathway (2013)
  • 著者名/発表者名: Goudarzi H, Iizasa H, Furuhashi M, Nakazawa S, Nakane R, Liang S, Hida Y, Yanagihara K, Kubo T, Nakagawa K, Kobayashi M, Irimura T, Hamada J
  • 雑誌名: Cancer Letter 巻: 339(1) ページ: 82-92
• [雑誌論文] Monocyte differentiation induced by co-culture with tumor cells involves RGD-dependent cell adhesion to extracellular matrix (2012)
  • 著者名/発表者名: Kamoshida G, Matsuda A, Sekine W, Mizuno H, Oku T, Itoh S, Irimura T, Tsuji T
  • 雑誌名: Cancer Lett 巻: 315(2) ページ: 145-152
• [雑誌論文] Cell surface expression of hyaluronan on human ovarian cancer cells inversely correlates with their adhesion to peritoneal mesothelial cells (2012)
  • 著者名/発表者名: Tamada Y, Takeuchi H, Suzuki N, Aoki D, Irimura T
  • 雑誌名: Tumour Biol 巻: 33(4) ページ: 1215-1222
• [雑誌論文] Targeting of macrophage galactose-type C-type lectin (MGL) induces DC signaling and activation (2012)
  • 著者名/発表者名: Napoletano C, Zizzari IG, Rughetti A, Rahimi H, Irimura T, Clausen H, Wandall HH, Belleudi F, Bellati F, Pierelli L, Frati L, Nuti M
  • 雑誌名: Eur J Immunol 巻: 42(4) ページ: 936-945
• [雑誌論文] Mucin 21 in esophageal squamous epithelia and carcinomas : analysis with glycoform-specific monoclonal antibodies (2012)
  • 著者名/発表者名: Tian Y, Denda-Nagai K, Kamata-Sakurai M, Nakamori S, Tsukui T, Itoh Y, Okada K, Yi Y, Irimura T
  • 雑誌名: Glycobiology 巻: 22(9) ページ: 1218-1226
• [雑誌論文] Establishment of PI3K inhibitor-resistant cancer cell lines and the therapeutic strategies for overcoming the resistance (2012)
  • 著者名/発表者名: Isoyama S, Dan S, Nishimura Y, Nakamura N, Kajiwara G, Seki M, Irimura T, Yamori T
  • 雑誌名: Cancer Sci 巻: 103(11) ページ: 1955-1960
• [雑誌論文] Development of an immunohistochemical protein quantification system in conjunction with tissue microarray technology for identifying predictive biomarkers for phosphatidylinositol 3-kinase inhibitors (2012)
  • 著者名/発表者名: Isoyama S, Yoshimi H, Dan S, Okamura M, Seki M, Irimura T, Yamori T
  • 雑誌名: Biol Pharm Bull 巻: 35(9) ページ: 1607-1613
• [雑誌論文] Local effects of regulatory T cells in MUC1 transgenic mice potentiate growth of MUC1 expressing tumor cells in vivo (2012)
  • 著者名/発表者名: Sugiura D, Denda-Nagai K, Takashima M, Murakami R, Nagai S, Takeda K, Irimura T
  • 雑誌名: PLoS One 巻: 7(9) ページ: e44770
• [雑誌論文] Cytokine Secretion from Human Monocytes Potentiated by P-Selectin-Mediated Cell Adhesion (2012)
  • 著者名/発表者名: Suzuki J, Hamada E, Shodai T, Kamoshida G, Kudo S, Itoh S, Koike J, Nagata K, Irimura T, Tsuji T
  • 雑誌名: Int Arch Allergy Immunol 巻: 160(2) ページ: 152-160
• [雑誌論文] Expression and the role of 3'-phosphoadenosine 5'-phosphosulfate transporters in human colorectal carcinoma (2011)
  • 著者名/発表者名: Kamiyama S, Ichimiya T, Ikehara Y, Takase T, Fujimoto I, Suda T, Nakamori S, Nakamura M, Nakayama F, Irimura T, Nakanishi H, Watanabe M, Narimatsu H, Nishihara S
  • 雑誌名: Glycobiology 巻: 21(2) ページ: 235-246
• [雑誌論文] Involvement of viral envelope GP2 in Ebola virus entry into cells expressing the macrophage galactose-type C-type lectin (2011)
  • 著者名/発表者名: Usami K, Matsuno K, Igarashi M, Denda-Nagai K, Takada A, Irimura T
  • 雑誌名: Biochem Biophys Res Commun 巻: 407(1) ページ: 74-78
• [雑誌論文] Early activation and interferon-γproduction of tumor-infiltrating mature CD27 high natural killer cells (2011)
  • 著者名/発表者名: Hayakawa Y, Sato-Matsushita M, Takeda K, Iwakura Y, Tahara H, Irimura T
  • 雑誌名: Cancer Sci 巻: 102(11) ページ: 1967-1971
• [雑誌論文] Asialoglycoprotein receptor promotes cancer metastasis by activating the EGFR-ERK pathway (2011)
  • 著者名/発表者名: Ueno S, Mojic M, Ohashi Y, Higashi N, Hayakawa Y, Irimura T
  • 雑誌名: Cancer Res 巻: 71(20) ページ: 6419-6427
• [雑誌論文] Distribution and function of macrophage galactose-type C-type lectin 2 (MGL2/CD301b) (2010)
  • 著者名/発表者名: Denda-Nagai K, Aida S, Saba K, Suzuki K, Moriyama S, Oo-Puthinan S, Tuiji M, Morikawa A, Kumamoto Y, Sugiura D, Kudo A, Akimoto Y, Kawakami H, Bovin NV, Irimura T
  • 雑誌名: J Biol Chem 巻: 285(25) ページ: 19193-19204
• [雑誌論文] Organ microenvironment plays significant roles through Fas ligand in vaccine-induced CD4 T cell dependent suppression of tumor growth at the orthotopic site (2010)
  • 著者名/発表者名: Sugiura D, Denda-Nagai K, Takeda K, Irimura T
  • 雑誌名: Cancer Sci 巻: 101(9) ページ: 1965-1969
• [雑誌論文] Mucin 21/epiglycanin modulates cell adhesion (2010)
  • 著者名/発表者名: Yi Y, Kamata-Sakurai M, Denda-Nagai K, Itoh T, Okada K, Ishii-Schrade K, Iguchi A, Sugiura D, Irimura T
  • 雑誌名: J Biol Chem 巻: 285(28) ページ: 21233-21240
• [雑誌論文] Loss of UDP-GalNAc : Polypeptide N-acetylgalactosaminyltransferase3 and reduced O-glycosylation in colon carcinoma cells selected for hepatic metastasis (2010)
  • 著者名/発表者名: Kato K, Takeuchi H, Kanoh A, Miyahara N, Nemoto-Sasaki Y, Morimoto-Tomita M, Matsubara A, Ohashi Y, Waki M, Usami K, Mandel U, Clausen H, Higashi N, Irimura T
  • 雑誌名: Glycoconj J 巻: 27 ページ: 267-276
• [雑誌論文] Wisteria floribunda agglutinin-positive mucin 1 is a sensitive biliary marker for human cholangiocarcinoma (2010)
  • 著者名/発表者名: Matsuda A, Kuno A, Kawamoto T, Matsuzaki H, Irimura T, Ikehara Y, Zen Y, Nakanuma Y, Yamamoto M, Ohkohchi N, Shoda J, Hirabayashi J, Narimatsu H
  • 雑誌名: Hepatology 巻: 52(1) ページ: 174-182
• [雑誌論文] Different potential of C-type lectin-mediated entry between Marburg virus strains (2010)
  • 著者名/発表者名: Matsuno K, Kishida N, Usami K, Igarashi M, Yoshida R, Nakayama E, Shimojima M, Feldmann H, Irimura T, Kawaoka Y, Takada
  • 雑誌名: J Virol 巻: 84(10) ページ: 5140-5147
• [雑誌論文] Macrophage receptors for influenza A virus : role of the macrophage galactose-type lectin and mannose receptor in viral entry (2010)
  • 著者名/発表者名: Upham JP, Pickett D, Irimura T, Anders EM, Reading PC
  • 雑誌名: J Virol 巻: 84(8) ページ: 3730-3737
• [雑誌論文] C-type lectins do not act as functional receptors for filovirus entry into cells (2010)
  • 著者名/発表者名: Matsuno K, Nakayama E, Noyori O, Marzi A, Ebihara H, Irimura T, Feldmann H, Takada A
  • 雑誌名: Biochem Biophys Res Commun 巻: 403(1) ページ: 144-148
• [学会発表] Roles of heparanase expression in local and systemic inflammation (2012)
  • 著者名/発表者名: Shida H, Sue M, Komatsu N, Waki M, Nishimura Y, Nakajima M, Higashi N, Irimura T
  • 学会等名: International Symposium on Glyco-minded Biology of Diseases as a Basis of Pharmaceutical Sciences
  • 発表場所: Ito Memorial Hall, The University of Tokyo, Tokyo(11/30 P)
  • 年月日: 20121130-1201
• [学会発表] MUC1 glycoforms have impact on protective immunity against MUC1-expressing tumor cells through the function of antigen presenting cells bearing MGL1/MGL2 (2012)
  • 著者名/発表者名: Kimura A, Denda-Nagai K, Irimura T
  • 学会等名: International Symposium on Glyco-minded Biology of Diseases as a Basis of Pharmaceutical Sciences
  • 発表場所: Ito Memorial Hall, The University of Tokyo, Tokyo(11/30)
  • 年月日: 20121130-1201
• [学会発表] IL-17-producing NK1.1+ CD27+γδT cells promote tumor malignant progression by inducing inflammatory microenvironment (2012)
  • 著者名/発表者名: Kimura Y, Sato-Matsushita M, Tahara H, Irimura T, Hayakawa Y
  • 学会等名: International Symposium on Glyco-minded Biology of Diseases as a Basis of Pharmaceutical Sciences
  • 発表場所: Ito Memorial Hall, The University of Tokyo, Tokyo(11/30)
  • 年月日: 20121130-1201
• [学会発表] Bioluminescent imaging of inflammatory tissue microenvironment in 4T1 breast cancer model (2012)
  • 著者名/発表者名: Takahashi K, Irimura T, Hayakawa Y
  • 学会等名: International Symposium on Glyco-minded Biology of Diseases as a Basis of Pharmaceutical Sciences
  • 発表場所: Ito Memorial Hall, The University of Tokyo, Tokyo(11/30)
  • 年月日: 20121130-1201
• [学会発表] Characterization of gene expression profiles of early or late progressor cancer cells in inflammation-associated malignant progression model (2012)
  • 著者名/発表者名: Nagai N, Tsunekawa N, Kimura Y, Irimura T, Hayakawa Y
  • 学会等名: International Symposium on Glyco-minded Biology of Diseases as a Basis of Pharmaceutical Sciences
  • 発表場所: Ito Memorial Hall, The University of Tokyo, Tokyo
  • 年月日: 20121130-1201
• [学会発表] Bioluminescent imaging of inflammatory tissue microenvironment in 4T1 breast cancer model (2012)
  • 著者名/発表者名: Takahashi K, Irimura T, Hayakawa Y
  • 学会等名: International Symposium on Glyco-minded Biology of Diseases as a Basis of Pharmaceutical Sciences
  • 発表場所: Ito Memorial Hall, The University of Tokyo, Tokyo
  • 年月日: 20121130-1201
• [学会発表] Dermal dendritic cells expressing MGL2 skew the immune response toward Th2 in contact hypersensitivity (2012)
  • 著者名/発表者名: Denda-Nagai K, Murakami R, Hashimoto S, Nagai S, Irimura T
  • 学会等名: The 12th International Symposium on Dendritic Cells
  • 発表場所: Daegu, Korea(10/11)
  • 年月日: 20121007-11
• [学会発表] Esophageal squamous carcinoma and normal squamous epithelia express differentially glycosylated mucin 21 (2012)
  • 著者名/発表者名: Tian Y, Denda-Nagai K, Kamata-Sakurai M, Nakamori S, Irimura T
  • 学会等名: 14th International Biennial Conference on Metastasis Research 2012
  • 発表場所: Brisbane Convention and Exhibition Centre, Cnr Merivale and Glenelg Streets, South Bank, Brisbane, Queensland, Australia(9/3, P)
  • 年月日: 20120902-05
• [学会発表] IL-17-producing NK1.1–CD27–gd T cells promote tumor malignant progression by inducing inflammatory microenvironment (2012)
  • 著者名/発表者名: Kimura Y, Sato-Matsushita M, Tahara H, Irimura T, Hayakawa Y
  • 学会等名: 20th International Symposium on Molecular Cell Biology of Macrophages 2012
  • 発表場所: Sanjo Conference Hall, The University of Tokyo
  • 年月日: 20120615-16
• [学会発表] IL-10 induction in colonic macrophages by commensal bacteria is dependent on MGL1 and mediated by the Syk-CARD9 pathway (2012)
  • 著者名/発表者名: Denda-Nagai K, Kurashina R, Hara, Naoki Yoshida H, Irimura T
  • 学会等名: 20 th International Symposium on Molecular Cell Biology of Macrophages 2012
  • 発表場所: Sanjo Conference Hall, The University of Tokyo(6/15)
  • 年月日: 20120615-16
• [学会発表] A Unique dermal dendritic cell subset expressing macrophage galactose-type C-type lectin 2 (MGL2/CD301b) (2012)
  • 著者名/発表者名: Murakami R, Denda-Nagai K, Hashimoto S, Irimura T
  • 学会等名: Program for Young Researcher Symposium in Europe, supported by Graduate School of Pharmaceutical Sciences, U-Tokyo
  • 発表場所: University of Oxford, UK; University of Bonn, Germany(6/8, 6/11)
  • 年月日: 20120606-14
• [学会発表] Glycosylation of Ebola viral envelope glycoproteins : regulation and roles in the infection (2012)
  • 著者名/発表者名: Fujihira H, Usami K, Denda-Nagai K, Yamada K, Matsuno K, Shinohara Y, Takada A, Kakehi K, Irimura T
  • 学会等名: Program for Young Researcher Symposium in Europe supported by Graduate School of Pharmaceutical Sciences
  • 発表場所: U-Tokyo(6/7,11, P)
  • 年月日: 20120606-14
• [学会発表] Asialoglycoprotein Receptor Promotes Lung Metastasis by Activating the EGFR-ERK Pathway (2011)
  • 著者名/発表者名: Irimura T, Ueno S, Mojic M, Ohashi Y, Higashi N, Hyakawa Y
  • 学会等名: 2011 Annual Conference of the Society for Glycobiology
  • 発表場所: The Westin Seattle, WA, USA(11/11)
  • 年月日: 20111109-12
• [学会発表] Mucin 21/epiglycanin as a potential marker and a determinant of malignant behavior of cancer cells."Mucins in health and disease (2011)
  • 著者名/発表者名: Irimura T
  • 学会等名: 11th International Workshop Carcinoma-associated Mucins
  • 発表場所: Robinson College, Cambridge, UK(7/13)
  • 年月日: 20110709-13
• [学会発表] NKG2A and NKG2C bindα2, 3-sialyated glycans and sulphated glycans."Mucins in health and disease (2011)
  • 著者名/発表者名: Xin X, Irimura T
  • 学会等名: 11th International Workshop Carcinoma-associated Mucins
  • 発表場所: Robinson College, Cambridge, UK(7/9-13)
  • 年月日: 20110709-13
• [学会発表] Altered resolution of peritoneal inflammation in MMP-9-deficient mice (2011)
  • 著者名/発表者名: Kolaczkowska E, Higashi N, Nishimura Y, Nakajima M, Irimura T, Opdenakker G
  • 学会等名: 10th World Congress on Inflammation (WCI2011)
  • 発表場所: Palais des Congres, Paris(6/27, P)
  • 年月日: 20110625-29
• [学会発表] Strain-dependent glycosylation of Ebola viral envelope glycoproteins determines their infectivity, note html formatting may not appear correctly (2010)
  • 著者名/発表者名: Fujihira H, Usami K, Denda-Nagai K, Irimura T
  • 学会等名: 2010 Annual Conference of the Society for Glycobiology
  • 発表場所: Tradewinds Island Grand Resort, FL, USA(11/10)
  • 年月日: 20101107-10
• [学会発表] (2010)
  • 著者名/発表者名: Denda-Nagai K, Irimura T
  • 学会等名: 2010 Annual Conference of the Society for Glycobiology
  • 発表場所: Tradewinds Island Grand Resort, FL, USA(11/8)
  • 年月日: 20101107-10
• [学会発表] Distribution and function of macrophage galactose-type C-type lectin 2(MGL2/CD301b) (2010)
  • 著者名/発表者名: Denda-Nagai K, Murakami R, Irimura T
  • 学会等名: 11^<th> International Symposium on Dendritic Cells in Fundamental and Clinical Immunology
  • 発表場所: Convention Centre, Lugano, Switzerland(9/28)
  • 年月日: 20100926-30
• [学会発表] Regulated expression of heparanase in neutrophil extravasation (2010)
  • 著者名/発表者名: Sue M, Higashi N, Nishimura Y, Nakajima M, Irimura T
  • 学会等名: 14^<th> International Congress of Immunology
  • 発表場所: The Kobe Convention Center Complex, Kobe, Japan(8/24)
  • 年月日: 20100822-27
• [学会発表] Roles of macrophage galactose-type C-type lectin 2(MGL2/CD301b)in the immune response (2010)
  • 著者名/発表者名: Denda-Nagai K, Irimura T
  • 学会等名: 14^<th> International Congress of Immunology
  • 発表場所: The Kobe Convention Center Complex, Kobe, Japan(8/24)
  • 年月日: 20100822-27
• [学会発表] Heparanase regulates immune cell functions (2010)
  • 著者名/発表者名: Higashi N, Waki M, Sue M, Kogane Y, Nishimura Y, Nakajima M, Irimura T
  • 学会等名: 25th International Carbohydrate Symposium (ICS2010)
  • 発表場所: Makuhari Messe, Chiba(8/5)
  • 年月日: 20100801-06
• [学会発表] Bresalier RS. Galectin-3 polymorphisms and response of human breast and colon cancer cells to apoptotic stimuli (2010)
  • 著者名/発表者名: Ueno S, San YJ, Mazurek N, Byrd JC, Irimura T, Bresalier RS
  • 学会等名: 8th Joint Conference of the AACR and JCA"Cancer Genomics, Epigenomics, and The Development of Novel Therapeutics
  • 発表場所: Hilton Waikoloa Village, Hawaii, USA(2/6)
  • 年月日: 20100205-09
• [学会発表] Effect of MUC1 plasmid DNA and BM-DCs vaccination in an experimental colon carcinogenesis in MUC1 transgenic mice (2010)
  • 著者名/発表者名: Murwanti R, Sugiura D, Denda-Nagai K, Kamata-Sakurai M, Irimura T
  • 学会等名: 8th Joint Conference of the AACR and JCA"Cancer Genomics, Epigenomics, and The Development of Novel Therapeutics
  • 発表場所: Hilton Waikoloa Village, Hawaii, USA(2/6)
  • 年月日: 20100205-09