Immune-suppressive function of cancer-associated mucin epiglycanin/Muc21

2013 Fiscal Year Final Research Report

• Project/Area Number: 21390018
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: The University of Tokyo
• Principal Investigator: IRIMURA Tatsuro 東京大学, 薬学研究科(研究院), 名誉教授 (80092146)
• Project Period (FY): 2009-04-01 – 2013-03-31
• Keywords: ムチン / 免疫抑制 / がん / エピグリカニン / アポトーシス

Research Abstract

Biological and immunological behaviors of transfectants with mouse or human epiglycanin/MUC21 were investigated and the contribution of glycoforms was assessed. Tansfectants of mouse Muc21 were shown to be less adherent than mock transfectants to culture substrates and extracellular matrix components. These properties were due to interference of integrin functions. The transfectants were less sensitive to treatment with cytotoxic effects. These properties may explain the reason why cells with high Muc21 expression were resistant to immunological cancer surveillance. Similar properties such as resistance to apoptosis were observed with cells transfected with human MUC21.

Research Products

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