MUC21 glycoforms as the target of cancer diagnosis and therapy

• Project/Area Number: 25293011
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Juntendo University (2016); St. Luke's International University (2014-2015); The University of Tokyo (2013)
• Principal Investigator: IRIMURA Tatsuro 順天堂大学, 医学部, 特任教授 (80092146)
• Co-Investigator(Kenkyū-buntansha): 伝田 香里 順天堂大学, 医学部, 助教 (00313122)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000); Fiscal Year 2015: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2014: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2013: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
• Keywords: ムチン / 乳腺がん / 治療抵抗性 / モノクローナル抗体 / グライコフォーム / MUC21 / 腫瘍マーカー / 乳がん / 糖鎖 / がん / アポトーシス / 抗がん剤

Outline of Final Research Achievements

Expression of MUC21 gene and its glycosylated gene products was examined with breast carcinoma cells and tissue specimens with a variety of subtypes. It was found that MUC21 expression was associated with poor therapeutic outcomes among triple negative breast carcinoma patients but whether any association with the expression of particular glycoform of MUC21 is still unknown. An experimental system to investigate the contribution of interaction between MUC21 and galectin 3 in modulating apoptotic pathways was successfully established.

Research Products

• [Int'l Joint Research] Jagiellonian University(Poland)
• [Int'l Joint Research] UT-MD Anderson Cancer Center(USA)
• [Journal Article] Mesenchymal stem cells cultured under hypoxia escape from senescence via down-regulation of p16 and extracellular signal regulated kinase (2018)
  • Author(s): Ikedo T, Minami M, Kataoka H, Hayashi K, Nagata M, Fujikawa R, Yamazaki F, Setou M, Yokode M, Miyamoto S.
  • Journal Title: Biochem. Biophys. Res. Commun Volume: 495 Pages: 1259-1264
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Proteasome Inhibitor Loaded Micelles Enhance Antitumor Activity Through Macrophage Reprogramming by NF-κB Inhibition (2017)
  • Author(s): Hailiang Wu, Anqi Tao, John D. Martin, Sabina Quader, Xueying Liu, Kei Takahashi, Louise Hespel, Yutaka Miura, Yoshihiro Hayakawa, Tatsuro Irimura, Horacio Cabral, Kazunori Kataoka
  • Journal Title: J Pharm Sci Volume: - Pages: 2438-2446
  • DOI: 10.1016/j.xphs.2017.03.031
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Heparanase augments inflammatory chemokine production from colorectal carcinoma cell lines (2016)
  • Author(s): Tsunekawa N, Higashi N, Kogane Y, Waki M, Shida H, Nishimura Y, Adachi H, Nakajima M, Irimura T
  • Journal Title: Biochem Biophys Res Commun. Volume: 469 Pages: 878-883
  • DOI: 10.1016/j.bbrc.2015.12.074
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Report on the use of non-clinical studies in the regulatory evaluation of oncology drugs. (2016)
  • Author(s): Hayakawa Y, Kawada M, Nishikawa H, Ochiya T, Saya H, Seimiya H, Yao Y, Hayashi M, Kai C, Matsuda A, Naoe T, Ohtsu A, Okazaki T, Saji H, Sata M, Sugimura H, Sugiyama Y, Toi M, Irimura T
  • Journal Title: Cancer Sci. Volume: 107(2) Pages: 189-202
  • DOI: 10.1111/cas.12857
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] An iminosugar-based heparanase inhibitor heparastatin (SF4) suppresses infiltration of neutrophils and monocytes into inflamed dorsal air pouches (2016)
  • Author(s): Sue M, Higashi N, Shida H, Kogane Y, Nishimura Y, Adachi H, Kolaczkowska E, Kepka M, Nakajima M, Irimura T.
  • Journal Title: Int Immunopharmacol. Volume: 35 Pages: 15-21
  • DOI: 10.1016/j.intimp.2016.03.017
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] IL-17A-producing CD30+ Vδ1 T cells drive inflammation-induced cancer progression (2016)
  • Author(s): Kimura Y, Nagai N, Tsunekawa N, Sato-Matsushita M, Yoshimoto T, Cua DJ, Iwakura Y, Yagita H, Okada F, Tahara H, Saiki I, Irimura T, Hayakawa Y.
  • Journal Title: Cancer Sci Volume: 107 Pages: 1106-1214
  • DOI: 10.1111/cas.13005
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Irsogladine maleate regulates the inflammatory related genes in human gingival epithelial cells stimulated by Aggregatibacter actinomycetemcomitans. (2016)
  • Author(s): Sue M, Higashi N, Shida H, Kogane Y, Nishimura Y, Adachi H, Kolaczkowskad , Kepka EMA, Nakajima M, Irimura T.
  • Journal Title: International Immunopharmacology Volume: 35 Pages: 5-21
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] A disintegrin and metalloenzyme (ADAM) 17 activation is regulated by α5β1 integrin in kidney mesangial cells. (2016)
  • Author(s): Waku, D., Segawa, T., Yonezawa, T., Akiyoshi, A., Ishige, T., Ueda, M., Ogawa, H., Sasaki, H., Ando, M., Kohno, N., Sasaki, T.
  • Journal Title: PLos One Volume: 11 Pages: 9-12
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Mammary tissue microenvironment determines T cell-dependent breast cancer-associated inflammation (2015)
  • Author(s): Takahashi K, Nagai N, Ogura K, Tsuneyama K, Saiki I, Irimura T, Hayakawa Y.
  • Journal Title: Cancer Science Volume: 106 Pages: 867-874
  • DOI: 10.1111/cas.12685
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Lectin microarray-based sero-biomarker verification targeting aberrant O-linked glycosylation on mucin 1 (2015)
  • Author(s): Matsuda A, Kuno A, Nakagawa T, Ikehara Y, Irimura T, Yamamoto M, Nakanuma Y, Miyoshi E, Nakamori S, Nakanishi H, Viwatthanasittiphong C, Srivatanakul P, Miwa M, Shoda J, Narimatsu H
  • Journal Title: Anal Chem Volume: 87(14) Pages: 7274-7281
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] POMGNT1 Is Glycosylated by Mucin-Type <i>O</i>-Glycans (2015)
  • Author(s): Xin X, Akasaka-Manya K, Manya H, Furukawa J, Kuwahara N, Okada K, Tsumoto H, Higashi N, Kato R, Shinohara Y, Irimura T, Endo T.
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 38 Issue: 9 Pages: 1389-1394
  • DOI: 10.1248/bpb.b15-00415
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] 免疫系とバイオマテリアル：総論 (2015)
  • Author(s): 入村達郎、伝田香里
  • Journal Title: Biomaterials Volume: 33(2) Pages: 8-15
  • Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] CXCL16 suppresses liver metastasis of colorectal cancer by promoting TNF-α-induced apoptosis by tumor-associated macrophages (2015)
  • Author(s): Kee JY, Ito A, Hojo S, Hashimoto I, Igarashi Y, Tsuneyama K, Tsukada K, Irimura T, Shibahara N, Takasaki I, Inujima A, Nakayama T, Yoshie O, Sakurai H, Saiki I, Koizumi K.
  • Journal Title: BMC Cancer Volume: in press Pages: 1471-1472
  • DOI: 10.1186/1471-2407-14-949
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Mammary tissue microenvironment determines T cell-dependent breast cancer-associated inflammation. (2015)
  • Author(s): Takahashi K, Nagai N, Ogura K, Tsuneyama K, Saiki I, Irimura T, Hayakawa Y.
  • Journal Title: Cancer Sci Volume: 15
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] The macrophage galactose-type lectin can function as an attachment and entry receptor for influenza virus. (2014)
  • Author(s): Ng WC, Liong S, Tate MD, Irimura T, Denda-Nagai K, Brooks AG, Londrigan SL, Reading PC.
  • Journal Title: J Virol Volume: 88(3) Pages: 1659-1672
  • DOI: 10.1128/jvi.02014-13
  • Peer Reviewed / Open Access
• [Journal Article] Heparanase-mediated cleavage of macromolecular heparin accelerates release of granular components of mast cells from extracellular matrices. (2014)
  • 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: Biochemical Journal Volume: 458(2) Pages: 291-299
  • DOI: 10.1042/bj20131463
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Up-regulation of neogenin-1 increases cell proliferation and motility in gastric cancer. (2014)
  • Author(s): Kim SJ, Wang YG, Lee HW, Kang HG, La SH, Choi IJ, Irimura T, Ro JY, Bresalier RS, Chun KH.
  • Journal Title: Oncotarget Volume: 5(10) Pages: 3386-2298
  • Peer Reviewed / Open Access
• [Journal Article] Interaction of Muc4 and ErbB2 in a transgenic mouse model of gallbladder carcinoma: potential pathobiological implications. (2014)
  • Author(s): Miyahara N, Shoda J, Kawamoto T, Ishida H, Ueda T, Akimoto Y, Kawakami H, Irimura T.
  • Journal Title: Oncol Rep Volume: 32(5) Pages: 1796-1802
  • DOI: 10.3892/or.2014.3443
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Identification of Hirsutine as an anti-metastatic phytochemical by targeting NF-κB activation (2014)
  • Author(s): Chenghua Lou, Kei Takahashi, Tatsuro Irimura, Ikuo Saiki and Yoshihiro Hayakawa
  • Journal Title: Int J Oncol. Volume: 45 Pages: 2085-1091
  • DOI: 10.3892/ijo.2014.2624
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Use of the γ-H2AX assay to monitor DNA damage and repair in translational cancer research (2014)
  • Author(s): Haruta M, Kamijo T, Nakagawara A, Kaneko Y.
  • Journal Title: Cancer Letters Volume: 348 Pages: 123133-123133
  • Peer Reviewed / Open Access
• [Journal Article] A unique dermal dendritic cell subset that skews the immune response toward Th2. (2013)
  • Author(s): Kei Takahashi, Kazuyoshi Takeda, Ikuo Saiki, Tatsuro Irimura and Yoshihiro Hayakawa
  • Journal Title: Plos One Volume: 104 Pages: 558-562
  • DOI: 10.1111/cas.12112
  • Peer Reviewed
• [Presentation] ムチン21とその糖鎖: がんによる免疫抑制とアポトーシスの制御に関わるムチン (2017)
  • Author(s): 入村達郎
  • Organizer: 糖鎖免疫シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2017-01-25
  • Invited
• [Presentation] Future of Glycobiologics (2016)
  • Author(s): Tatsuro Irimura
  • Organizer: Frontier 2016-UT/EPFL Joint Symposium
  • Place of Presentation: Lausanne
  • Year and Date: 2016-12-05
  • Int'l Joint Research / Invited
• [Presentation] MUC1 with truncated O-glycans induces humoral immune responses and suppresses the carcinoma growth and metastasis (2015)
  • Author(s): Kaori Denda-Nagai, Tatsuro Irimura
  • Organizer: 第44回日本免疫学会学術集会
  • Place of Presentation: 札幌コンベンションセンター
  • Year and Date: 2015-11-20
  • Int'l Joint Research / Invited
• [Presentation] C-Type Lectins on Dendritic Cell and Macrophages Regulate Infection and Immunity (2015)
  • Author(s): Irimura Tatsuro
  • Organizer: LMU-UT Symposium
  • Place of Presentation: Munich, Germany
  • Year and Date: 2015-10-28
  • Int'l Joint Research / Invited
• [Presentation] エボラウィルス-MGL相互作用の謎 (2015)
  • Author(s): 藤平陽彦、宇佐美克明、伝田香里、古川潤一、篠原康郎、松野啓太、高田礼人、河岡義裕、入村達郎
  • Organizer: 糖鎖免疫シンポジウム
  • Place of Presentation: 東京医科歯科大学（東京）
  • Year and Date: 2015-08-19
  • Invited
• [Presentation] がん悪性化進展を促す炎症性免疫応答の維持機構におけるIL-17の重要性 (2015)
  • Author(s): 早川芳弘、永井直、斉木育夫、入村達郎
  • Organizer: 第24回日本がん転移学会
  • Place of Presentation: シティプラザ大阪（大阪）
  • Year and Date: 2015-07-24
  • Invited
• [Presentation] MGL(CD301)in infection and immunity (2015)
  • Author(s): Irimura Tatsuro
  • Organizer: International Workshop on Mucins in Health and diseases
  • Place of Presentation: Cambridge, UK
  • Year and Date: 2015-07-21
  • Int'l Joint Research / Invited
• [Presentation] 薬科学に未来はあるか (2015)
  • Author(s): 入村達郎
  • Organizer: 日本薬剤会第30回記念大会
  • Place of Presentation: 長崎ブリックホール（長崎）
  • Year and Date: 2015-05-23
  • Invited
• [Presentation] 糖鎖付加MUC1に対する免疫応答による癌の増殖と転移の制御 (2015)
  • Author(s): 難波愛理、伝田香里、野地美樹、入村達郎
  • Organizer: 第135日本薬学会年会
  • Place of Presentation: 神戸
  • Year and Date: 2015-03-25 – 2015-03-28
• [Presentation] Heparanase-mediated cleavage of macromolecular heparin accelerates release of granular components of mouse peritoneal cell-derived mast cells. (2014)
  • Author(s): 東伸昭，入村達郎
  • Organizer: 第43回日本免疫学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] マクロファージガラクトース型C型レクチン（MGL/CD301）による炎症と免疫の制御 (2014)
  • Author(s): 伝田香里、入村達郎
  • Organizer: 第12回糖鎖科学コンソーシアムシンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2014-12-04 – 2014-12-05
  • Invited
• [Presentation] Identification of Hirsutine as an anti-metastatic phytochemical by targeting NF-κB activation. (2014)
  • Author(s): Lou C, Takahashi K, Irimura T, Saiki I, Hayakawa Y.
  • Organizer: 第73回日本癌学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] A unique dermal dendritic cell subset that skews the immune response toward Th2. (2014)
  • Author(s): Irimura T.
  • Organizer: MGH and U-Tokyo Joint Symposium on Frontiers in Biomedical Engineering
  • Place of Presentation: Cambridge, MA, USA
  • Year and Date: 2014-09-24 – 2014-09-25
• [Presentation] Public private partnership in Japanese pharmaceutical affairs. (2014)
  • Author(s): Irimura T.
  • Organizer: FIP Congress
  • Place of Presentation: Bangkok, Thailand
  • Year and Date: 2014-08-31 – 2014-09-04
  • Invited
• [Presentation] マスト細胞顆粒内ヘパリンの切断は細胞外マトリックスからの生理活性物質の放出を促進する (2014)
  • Author(s): 東伸昭，中島元夫、入村達郎
  • Organizer: 第33回日本糖質学会
  • Place of Presentation: 名古屋
  • Year and Date: 2014-08-10 – 2014-08-12
• [Presentation] Vd1T細胞を起点とする自然炎症はがん悪性化を促進する (2014)
  • Author(s): 早川芳弘、済木育夫、入村達郎
  • Organizer: 第23回がん転移学会学術集会
  • Place of Presentation: 金沢
  • Year and Date: 2014-07-10 – 2014-07-11
  • Invited
• [Presentation] Requirement of CD4T cells for establishing inflammatory tumor microenvironment in 4T1breast cancer model. (2014)
  • Author(s): Takahashi K, Nagai N, Saiki I, Irimura T, Hayakawa Y.
  • Organizer: The 22nd International Symposium on Molecular Cell Biology of Macrophages.
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2014-06-02 – 2014-06-03
• [Presentation] Differential glycosylation of MUC1 has an impact on cancer immunity through the function of MGL1/MGL2 (2013)
  • Author(s): 木村翔彦、伝田-永井 香里、入村達郎
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜、横浜
• [Presentation] がん悪性化進展を促進するgdT17 細胞を起点とした炎症性微小環境は宿主―がん細胞相互作用により増強される (2013)
  • Author(s): 木村好孝、松下（佐藤）まりも、善本隆之、田原秀晃、済木育夫、入村達郎、早川芳弘
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜、横浜
• [Presentation] がん悪性化進展モデルにおける炎症性微小環境のがん悪性化形質獲得に与える影響 (2013)
  • Author(s): 永井直、済木育夫、入村達郎、早川芳弘
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜、横浜
• [Presentation] 4T1乳がんモデルでの炎症性腫瘍微小環境形成におけるCD4陽性T細胞の重要性 (2013)
  • Author(s): 高橋恵生、永井直、常山幸一、済木育夫、入村達郎、早川芳弘
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜、横浜
• [Presentation] 生物発光イメージングによるマウス4T1細胞の腫瘍微小環境における転写因子NFkBを介した炎症性シグナル活性化の時空間的解析
  • Author(s): 髙橋恵生、永井直、済木育夫、入村達郎、早川芳弘
  • Organizer: 第17回がん分子標的治療学会学術集会
  • Place of Presentation: 国立京都国際会館・京都
• [Presentation] マウス4T1乳がんモデルでの炎症性腫瘍微小環境形成におけるCD4陽性T細胞の重性
  • Author(s): 高橋恵生、永井直、済木育夫、入村達郎、早川芳弘
  • Organizer: 第22回日本がん転移学会学術集会
  • Place of Presentation: ホテルブエナビスタ松本・松本
• [Presentation] 結腸がんの転移微小環境におけるヘパラナーゼ：ケモカイン産生誘導における役割
  • Author(s): 恒川直輝、東伸昭、中島元夫、入村達郎
  • Organizer: 第22回日本がん転移学会学術集会
  • Place of Presentation: ホテルブエナビスタ松本・松本
• [Presentation] がん悪性化進展モデルにおける炎症性美装環境のがん悪性化形質獲得に与える影響
  • Author(s): 永井直、入村達郎、早川芳弘
  • Organizer: 第22回日本がん転移学会学術集会
  • Place of Presentation: ホテルブエナビスタ松本・松本
• [Presentation] ヘパラナーゼは結腸がん細胞株に作用し転移関連分子の発現を誘導する
  • Author(s): 恒川直輝、東伸昭、中島元夫、入村達郎
  • Organizer: 第32回日本糖質学会年会
  • Place of Presentation: 大阪国際交流センター・大阪
• [Presentation] 結腸がんの転移微小環境におけるヘパラナーゼの関与
  • Author(s): 恒川直輝、東伸昭、中島元夫、入村達郎
  • Organizer: 第18回日本病態プロテアーゼ学会学術集会
  • Place of Presentation: 千里ライフサイエンスセンター・大阪
• [Presentation] "MUC21 regulates apoptosis in a glycosylation dependent manner"
  • Author(s): Yuan Tian, Kaori Denda-Nagai, Toshihisa Ogawa, Tatsuro Irimura
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: パシフィコ横浜・横浜
• [Presentation] Cancer immune escalation process triggered by activation of gamma-delta T17 cells through MyD88/IL-23 cascade.
  • Author(s): Yoshitaka Kimura, Marimo Sato-Matsushita, Takayuki Yoshimoto, Hideaki Tahara, Ikuo Saiki, Tatsuro Irimura, Yoshihiro Hayakawa.
  • Organizer: 日本免疫学会学術集会2013
  • Place of Presentation: 幕張メッセ、千葉
• [Presentation] Heparanase in metastatic microenvironment of colon cancer: a potential inducer of chemokine production
  • Author(s): Naoki Tsunekawa, Nobuaki Higashi, Tatsuro Irimura.
  • Organizer: 日本免疫学会学術集会2013
  • Place of Presentation: 幕張メッセ、千葉
• [Presentation] Heparanase in metastatic microenvironment of colon cancer: a potential inducer of chemokine production.
  • Author(s): Naoki Tsunekawa, Nobuaki Higashi, Tatsuro Irimura.
  • Organizer: 日本免疫学会学術集会2013
  • Place of Presentation: 幕張メッセ、千葉
• [Book] C-Type Lectin Receptors in Immunity (2016)
  • Author(s): Kaori Denda-Nagai and Tatsuro Irimura
  • Publisher: Springer
• [Book] 基礎生命科学 (2014)
  • Author(s): 入村達郎
  • Total Pages: 190
  • Publisher: 培風館