Analysis of intercellular adhesion molecules expressed in cancer stem cells of a Tax-transgenic mouse ATL model

• Project/Area Number: 23790454
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Experimental pathology
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: SUZUKI Tadaki 国立感染症研究所, 感染病理部, 研究員 (30527180)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 疾患モデル動物 / 成人T 細胞白血病モデルマウス / 成人T細胞白血病 / HTLV-1 / TAX / 動物モデル / 癌幹細胞

Research Abstract

Adult T-cell leukemia (ATL) is a T-cell malignancy caused by human T lymphotropic virus type I. The HTLV-I transactivator, Tax, initiates ATL-like disease (mATL) both in Tax transgenic mice (Tax-Tg). Recently, the candidates CSCs of mATL were identified in splenic lymphomatous cells (SLCs). The candidate CSCs could consistently regenerate the original lymphoma, suggesting that the eradication of cancer stem cells will be necessary to improve the outcome of treatment for mATL. In this study, a proteomic approach was used to identify proteins differentially present in CSCs of mATL. The CSCs of mATL were analyzed by liquid chromatography tandem mass spectrometry to compare protein profiles in CSCs and no-CSCs. This comparative proteomic analysis revealed that expression of one membrane protein was increased in CSCs, which might become a new target of antibody-based therapy. Flowcytometry validated expression of the membrane protein. Taken together, the data presented provide a significant new protein-level insight into the biology of cancer stem cells of mATL, a key population of cells that are also involved in mATL development.

Research Products

• [Journal Article] HTLV-1 と白血病・リンパ腫 (2013)
  • Author(s): 鈴木 忠樹, 長谷川 秀樹
  • Journal Title: 病理と臨床 Volume: 31(2) Pages: 146-150
• [Journal Article] Lethal canine distemper virus outbreak in cynomolgus monkeys in Japan in 2008. (2013)
  • Author(s): Sakai K, Nagata N, Ami Y, Seki F, Suzaki Y, Iwata-Yoshikawa N, Suzuki T, Fukushi S, Mizutani T, Yoshikawa T, Otsuki N, Kurane I, Komase K, Yamaguchi R, Hasegawa H, Saijo M, Takeda M, Morikawa S.
  • Journal Title: J. Virol. Volume: 87 Issue: 2 Pages: 1105-1114
  • DOI: 10.1128/jvi.02419-12
  • Peer Reviewed
• [Journal Article] Intracellular transport of the measles virus ribonucleoprotein complex is mediated by Rab11A-positive recycling endosomes and drives virus release from the apical membrane of polarized epithelial cells. (2013)
  • Author(s): Nakatsu Y, Ma X, Seki F, Suzuki T, Iwasaki M, Yanagi Y, Komase K, Takeda M.
  • Journal Title: J Virol. Volume: 87(8) Issue: 8 Pages: 4683-4693
  • DOI: 10.1128/jvi.02189-12
  • Peer Reviewed
• [Journal Article] Gold Nanoparticles as a Vaccine Platform: Influence of Size and Shape on Immunological Responses in Vitro and in Vivo. (2013)
  • Author(s): Niikura K, Matsunaga T, Suzuki T, Kobayashi S, Yamaguchi H, Orba Y, Kawaguchi A, Hasegawa H, Kajino K, Ninomiya T, Ijiro K, Sawa H.
  • Journal Title: ACS Nano. Volume: in press
  • Peer Reviewed
• [Journal Article] HTLV－1と白血病・リンパ腫 (2013)
  • Author(s): 鈴木 忠樹、長谷川 秀樹
  • Journal Title: 病理と臨床 Volume: 31(2) Pages: 146-150
• [Journal Article] Spi-B is critical for plasmacytoid dendritic cell function and development (2012)
  • Author(s): Sasaki, K. Hoshino, T. Sugiyama, C. Yamazaki, T. Yano, A. Iizuka, H. Hemmi, T. Tanaka, M. Saito, M. Sugiyama, Y. Fukuda, T. Ohta, K. Sato, A. Ainai, T. Suzuki, H. Hasegawa, N. Toyama-Sorimachi, H. Kohara, T. Nagasawa, T. Kaisho
  • Journal Title: Blood Volume: 120 Issue: 24 Pages: 4733-4743
  • DOI: 10.1182/blood-2012-06-436527
  • Peer Reviewed
• [Journal Article] Role of JC virus agnoprotein in virion formation. (2012)
  • Author(s): Suzuki T, Semba S, Sunden Y, Orba Y, Kobayashi S, Nagashima K, Kimura T, Hasegawa H, Sawa H.
  • Journal Title: Microbiol Immunol Volume: 56(9) Issue: 9 Pages: 639-46
  • DOI: 10.1111/j.1348-0421.2012.00484.x
  • Peer Reviewed
• [Journal Article] Mucosal IgA responses in influenza virus infections ; thoughts for vaccine design. (2012)
  • Author(s): E. van Riet, A. Ainai, T. Suzuki, H. Hasegawa
  • Journal Title: Vaccine Volume: 30 Issue: 40 Pages: 5893-5900
  • DOI: 10.1016/j.vaccine.2012.04.109
  • Peer Reviewed
• [Journal Article] Inhibitory effects of an M2-specific monoclonal antibody on different strains of influenza A virus. (2012)
  • Author(s): Muto NA, Yoshida R, Suzuki T, Kobayashi S, Ozaki H, Fujikura D, Manzoor R, Muramatsu M, Takada A, Kimura T, Sawa H.
  • Journal Title: Jpn J Vet Res. Volume: 60(2-3) Pages: 71-83
  • Peer Reviewed
• [Journal Article] Characterization of neutralizing antibodies in adults after intranasal vaccination with an inactivated influenza vaccine (2012)
  • Author(s): A. Ainai, S. Tamura, T. Suzuki, R. Ito, H. Asanuma, T. Tanimoto, Y. Gomi, S. Manabe, T. Ishikawa, Y. Okuno, T. Odagiri, M. Tashiro, T. Sata, T. Kurata, H. Hasegawa
  • Journal Title: J. Med. Virol. Volume: 84(2) Issue: 2 Pages: 336-344
  • DOI: 10.1002/jmv.22273
  • Peer Reviewed
• [Journal Article] Virus capsid coating of gold nanoparticles via cysteine-Au interactions and their effective cellular uptakes (2012)
  • Author(s): Keita Nagakawa, Keinchi Niikura, Tadaki Suzuki, Yasutaka Matsuo, Manabu Igarashi, Hirofumi Sawa, Kuniharu Ijiro
  • Journal Title: Chemistry Letters Volume: 41 Issue: 1 Pages: 113-115
  • DOI: 10.1246/cl.2012.113
  • NAID: 10030222850
  • Peer Reviewed
• [Journal Article] Wild-type measles virus with the hemagglutinin protein of the edmonston vaccine strain retains wild-type tropism in macaques (2012)
  • Author(s): Takeuchi K., et al.
  • Journal Title: J.Virol. Volume: 86 Issue: 6 Pages: 3027-3037
  • DOI: 10.1128/jvi.06517-11
  • NAID: 120007137251
  • Peer Reviewed
• [Journal Article] Equine major histocompatibility complex class I molecules act as entry receptors that bind to equine herpesvirus-1 glycoprotein D. (2011)
  • Author(s): Sasaki M, Hasebe R, Makino Y, Suzuki T, Fukushi H, Okamoto M, Matsuda K, Taniyama H, Sawa H, Kimura T.
  • Journal Title: Genes Cells. Volume: 16(4) Issue: 4 Pages: 343-57
  • DOI: 10.1111/j.1365-2443.2011.01491.x
  • NAID: 120005652749
  • Peer Reviewed
• [Journal Article] A novel function of the N-terminal domain of PA in assembly of influenza A virus RNA polymerase. (2011)
  • Author(s): Suzuki T, Ainai A, Nagata N, Sata T, Sawa H, Hasegawa H.
  • Journal Title: Biochem Biophys Res Commun. Volume: 414(4) Pages: 719-26
  • Peer Reviewed
• [Presentation] 進行性多巣性白質脳症におけるJCウイルス後期蛋白質発現動態の免疫組織化学的検討 (2012)
  • Author(s): 鈴木 忠樹、片野 晴隆、佐藤 由子、澤 洋文、佐多 徹太郎、長谷川 秀樹
  • Organizer: 第101回日本病理学会総会
  • Place of Presentation: 東京
• [Presentation] インフルエンザウイルスRNAポリメラーゼ三量体形成機構の解析 (2012)
  • Author(s): 鈴木 忠樹
  • Organizer: ナノバイオ国際共同研究教育拠点第1回若手国内シンポジウム
  • Place of Presentation: 神戸
• [Presentation] Disruption of AP-3 complex mediated vesicular trafficking by the JC polyomavirus agnoprotein is fundamental to viroporin activity and virus replication (2012)
  • Author(s): Tadaki Suzuki, Yasuko Orba, Yoshinori Makino, Yuji Sunden, Yuki Okada, Takashi Kimura, Tetsutaro Sata, Hideki Hasegawa, William W. Hall, Hirofumi Sawa
  • Organizer: THE 34th NAITO CONFERENCE ON Infection, Immunity and their Control for Health: Mucosal Barrier, Pathogen and Vaccine
  • Place of Presentation: Sapporo, Japan
• [Presentation] JCウイルス後期蛋白質に対する特異抗体を用いた進行性多巣性白質脳症の免疫組織化学的診断法の比較検討 (2012)
  • Author(s): 鈴木 忠樹、片野 晴隆、大場 靖子、小林 進太郎、佐藤 由子、佐多 徹太郎、澤 洋文、長谷川 秀樹
  • Organizer: 第60回日本ウイルス学会学術集会
  • Place of Presentation: 大阪
• [Presentation] インフルエンザワクチン経鼻接種により鼻腔内に誘導される分泌型IgA抗体の性状解析 (2012)
  • Author(s): 鈴木 忠樹、川口 晶、相内 章、田村 愼一、伊藤 良、小田切 孝人、田代 眞人、長谷川 秀樹
  • Organizer: 第16回日本ワクチン学会学術集会
  • Place of Presentation: 横浜
• [Presentation] Comparative proteomic analysis of cancer stem cells in a Tax-transgenic (Tax-Tg) mouse model of adult T-cell leukemia/lymphoma (2011)
  • Author(s): Tadaki Suzuki, Akiko Okayama, Takahiro Tsuji, Akihide Ryo, Hisashi Hirano, Tetsutaro Sata, William W. Hall, Hideki Hasegawa
  • Organizer: The 15th International Conference on Human Retrovirology: HTLV and Related Retroviruses
  • Place of Presentation: Belgium
• [Presentation] Comparative proteomic analysis of cancer stem cells in a Tax-transgenic (Tax-Tg) mouse model of adult T-cell leukemia/lymphoma (2011)
  • Author(s): Tadaki Suzuki, Akiko Okayama, Takahiro Tsuji, Akihide Ryo, Hisashi Hirano, Tetsutaro Sata, William W. Hall, Hideki Hasegawa
  • Organizer: The 15th International Conference on Human Retrovirology: HTLV and Related Retroviruses,
  • Place of Presentation: Belgium
• [Presentation] 蛍光タンパク質再構成法を用いたインフルエンザRNAポリメラーゼの３量体形成機構の解析 (2011)
  • Author(s): 鈴木 忠樹、相内 章、永田 典代、澤 洋文、佐多 徹太郎、長谷川 秀樹
  • Organizer: 第25回インフルエンザ研究者交流の会シンポジウム
  • Place of Presentation: 富山
• [Presentation] Role of the N-Terminal Region of the PA Subunit in Nuclear Import and Assembly of Influenza A Virus RNA Polymerase (2011)
  • Author(s): Tadaki Suzuki, Akira Ainai, Noriyo Nagata, Tetsutaro Sata, Hideki Hasegawa
  • Organizer: International Union of Microbiological Societies (IUMS) XV International Congress of Virology,
  • Place of Presentation: Sapporo