Analysis and application of synovial sarcoma stem cell

• Project/Area Number: 16K08703
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Hokkaido University
• Principal Investigator: Kimura Taichi 北海道大学, 医学研究院, 特任助教 (90435959)
• Co-Investigator(Kenkyū-buntansha): 津田 真寿美 北海道大学, 医学研究院, 准教授 (30431307)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 滑膜肉腫 / 癌幹細胞 / クロマチンリモデリング / 稀少がん / 稀少癌 / 腫瘍

Outline of Final Research Achievements

As a result of cDNA microarray, we detected fifteen candidate genes, up-regulated in synovial sarcoma stem cells, and regulated under the control of SS18-SSX. We established knock-down cell-lines of two candidate genes by lentiviral shRNA. Furthermore, using mass-spectrometry analysis, we selected fifteen SS18-SSX-binding proteins specified by synovial sarcoma stem cells. We established the knock-down cell-line of one candidate gene by lentiviral shRNA. This cell-line exhibited marked growth retardation under the sphere-forming condition.

Academic Significance and Societal Importance of the Research Achievements

本研究にて我々は滑膜肉腫幹細胞の制御・維持機構に関与する可能性のある新規候補分子を同定した。このうちの一つはノックダウンによりスフィア形成条件でのみ有意に細胞増殖が抑制することから滑膜肉腫における幹細胞治療法の標的分子となりうる可能性が示唆された。また候補分子中にはSWI SNF型クロマチンリモデリング複合体と相互作用する分子が含まれている。クロマチンリモデリング機構が腫瘍幹細胞の発生、維持に関与するか否かは現状不明であり、新たな研究領域の発展につながる可能性が示唆される。滑膜肉腫は稀少がんであり、現状有効な治療法が存在しないため上記の知見は治療法の探索において社会的意義を有すると考えられる。

Research Products

• [Journal Article] A Clinicopathological Analysis of Six Autopsy Cases of Sudden Unexpected Death due to Infectious Aortitis in Patients with Aortic Tears (2018)
  • Author(s): Kato MI, Tanino MA, Miyazaki M, Kimura T, Ishida Y, Wang L, Tsuda M, Nishihara H, Nagashima K, Tanaka S
  • Journal Title: Internal Medicine Volume: 57 Issue: 10 Pages: 1375-1380
  • DOI: 10.2169/internalmedicine.8976-17
  • NAID: 130006734384
  • ISSN: 0918-2918, 1349-7235
  • Year and Date: 2018-05-15
  • Peer Reviewed / Open Access
• [Journal Article] Interferon inducible Mx1 protein is highly expressed in renal tissues from treatment-naiive lupus nephritis, but not in those under immunosuppressive treatment (2018)
  • Author(s): Shimizu Y, Yasuda S, Kimura T, Nishio S, Kono M, Ohmura K, Shimamura S, Kono M, Fujieda Y, Kato M, Oku K, Bohgaki T, Fukasawa Y, Tanaka S, Atsumi T
  • Journal Title: Mod Rheumatol. Volume: 28(4) Pages: 661-669
  • Peer Reviewed
• [Journal Article] Post-reperfusion hydrogen gas treatment ameliorates ischemia reperfusion injury in rat livers from donors after cardiac death: a preliminary study. (2018)
  • Author(s): Ishikawa T, Shimada S, Fukai M, Kimura T, Umemoto K, Shibata K, Fujiyoshi M, Fujiyoshi S, Hayasaka T, Kawamura N, Kobayashi N, Shimamura T, Taketomi A.
  • Journal Title: Surgery Today Volume: 48(12) Issue: 12 Pages: 1081-88
  • DOI: 10.1007/s00595-018-1693-0
  • Peer Reviewed
• [Journal Article] Interferon-inducible Mx1 protein is highly expressed in renal tissues from treatment-naiive lupus nephritis, but not in those under immunosuppressive treatment. (2017)
  • Author(s): Shimizu Y, Yasuda S, Kimura T, Nishio S, Kono M, Ohmura K, Shimamura S, Kono M, Fujieda Y, Kato M, Oku K, Bohgaki T, Fukasawa Y, Tanaka S, Atsumi T
  • Journal Title: Modern Rheumatology Volume: Epub ahead of print Issue: 4 Pages: 1-9
  • DOI: 10.1080/14397595.2017.1404711
  • Peer Reviewed
• [Journal Article] Disseminated toxoplasmosis after hematopoietic stem cell transplantation showing unusual magnetic resonance images. (2017)
  • Author(s): Tateno T, Onozawa M, Hashiguchi J, Ishio T, Yuzawa S, Matsuoka S, Kosugi-Kanaya M, Okada K, Shiratori S, Goto H, Kimura T, Sugita J, Nakagawa M, Hashimoto D, Kahata K, Fujimoto K, Endo T, Kondo T, Tanaka S, Hashino S, Teshima T
  • Journal Title: TRANSPLANT INFECTIOUS DISEASE Volume: 19 Issue: 4
  • DOI: 10.1111/tid.12720
  • Peer Reviewed
• [Journal Article] Clinicopathological evaluation of Sox10 expression in diffuse-type gastric adenocarcinoma (2017)
  • Author(s): 5.Kato, M., Nishihara, H., Hayashi, H., Kimura, T., Ishida, Y., Wang, L., Tsuda, M., Tanino, MA., Tanaka, S.
  • Journal Title: Med. Oncol. Volume: 34 Issue: 1 Pages: 8-8
  • DOI: 10.1007/s12032-016-0865-2
  • Peer Reviewed
• [Journal Article] Notch1 regulates invasion and metastasis of head and neck squamous cell carcinoma by inducing EMT through c-Myc. (2017)
  • Author(s): Inamura N, Kimura T, Wang L, Yanagi H, Tsuda M, Tanino M, Nishihara H, Fukuda S, Tanaka S.
  • Journal Title: Auris Nasus Larynx Volume: 44 Issue: 4 Pages: 447-457
  • DOI: 10.1016/j.anl.2016.08.003
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Novel signaling collaboration between TGF-beta and adaptor protein Crk facilitates EMT in human lung cancer (2016)
  • Author(s): Elmansuri AZ, Tanino MA, Mahabir R, Wang L, Kimura T, Nishihara H, Kinoshita I, Dosaka-Akita H, Tsuda M and Tanaka S
  • Journal Title: Oncotarget Volume: （in press） Issue: 19 Pages: 27094-107
  • DOI: 10.18632/oncotarget.8314
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Clinical impact of targeted amplicon sequencing for meningioma as a practical clinical-sequencing system. (2016)
  • Author(s): Yuzawa S, Nishihara H, Yamaguchi S, Mohri H, Wang L, Kimura T, Tsuda M, Tanino M, Kobayashi H, Terasaka S, Houkin K, Sato N, Tanaka S.
  • Journal Title: Mod Pathol. Volume: 29 Issue: 7 Pages: 708-16
  • DOI: 10.1038/modpathol.2016.81
  • NAID: 120005905622
  • Peer Reviewed / Open Access
• [Journal Article] Aldo-keto reductase 1C1 induced by interleukin-1beta mediates the invasive potential and drug resistance of metastatic bladder cancer cells. (2016)
  • Author(s): Matsumoto R, Tsuda M, Yoshida K, Tanino M, Kimura T, Nishihara H, Abe T, Shinohara N, Nonomura K, Tanaka S
  • Journal Title: Scientific reports Volume: 4 Issue: 1 Pages: 34625-34625
  • DOI: 10.1038/srep34625
  • Peer Reviewed / Open Access
• [Presentation] 高分子ハイドロゲルによる滑膜肉腫幹細胞誘導メカニズムの解析 (2018)
  • Author(s): 倉井毅、津田真寿美、王磊、木村太一、鈴鹿淳、青山佳代子、安田和則、剣萍、田中伸哉
  • Organizer: 第107回日本病理学会総会 2018.6.21-23 ロイトン札幌、ニトリ文化ホール、さっぽろ芸文館（札幌市）
• [Presentation] チロシンキナーゼ阻害剤耐性ヒト膠芽腫細胞におけるABC transporterの同定 (2016)
  • Author(s): 鍋島龍一、津田真寿美、鈴鹿淳、王磊、木村太一、谷野美智枝、田中伸哉
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（横浜市)
  • Year and Date: 2016-11-30
• [Presentation] AKR1C1 mediates bladder cancer metastasis and drug resistance. (2016)
  • Author(s): Masumi Tsuda, Ryuji Matsumoto, Kazuhiko Yoshida, Mishie Tanino, Taichi Kimura, Hiroshi Nishihara, Takashige Abe, Nobuo Shinohara, Katsuya Nonomura, Shinya Tanaka
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（横浜市）
  • Year and Date: 2016-10-06
• [Presentation] Clinical impact of targeted amplicon sequence for meningioma as a practical clinical sequence system. (2016)
  • Author(s): Hiroshi Nishihara, Sayaka Yuzawa, Shigeru Yamaguchi, Hiromi Mohri, Lei Wang, Taichi Kimura, Masumi Tsuda, Mishie Tanino, Hiroyuki Kobayashi, Shunsuke Terasaka, Kiyohiro Houkin, Shinya Tanaka
  • Organizer: Society for Neuro-Oncology Conference on Menigioma
  • Place of Presentation: the Yorkville InterContinental Hotel in Toronto（Ontario, Canada）
  • Year and Date: 2016-06-17
• [Presentation] 滑膜肉腫幹細胞の制御・維持機構の解明 (2016)
  • Author(s): 木村太一、王磊、津田真寿美、西原広史、田中伸哉
  • Organizer: 第105回日本病理学会総会
  • Place of Presentation: 仙台国際センター（仙台市）
  • Year and Date: 2016-05-12
• [Presentation] 卵巣癌に対するEZH2阻害剤とPaclitaxelの併用効果に関する検討 (2016)
  • Author(s): 遠藤大介、木村太一、渡利英道、櫻木範明、田中伸哉
  • Organizer: 第96回北海道医学大会（腫瘍系）分科会・第114回北海道癌談話会
  • Place of Presentation: 札幌医大記念ホール（札幌市）