Establishment of synovial sarcoma initiating cell model and exploration of new therapeutic targets

• Project/Area Number: 25460471
• 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(系)研究科(研究院), 特任助教 (90435959)
• Co-Investigator(Kenkyū-buntansha): TANAKA SHINYA 北海道大学, 医学研究科, 教授 (70261287) ; 谷野 美智枝 北海道大学, 医学(系)研究科(研究院), 講師 (90360908)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 滑膜肉腫 / 腫瘍幹細胞 / スフィア形成法 / SWI/SNF複合体 / 質量分析 / 癌幹細胞 / 間葉系幹細胞 / 腫瘍モデル

Outline of Final Research Achievements

In this study, to elucidate the maintenance and regulation mechanisms of synovial sarcoma initiating cells that are closely involved in the recurrence and metastasis, we examined SS18-SSX binding proteins which were specific for sphere-forming subpopulation by mass spectrometry analysis. By proteomic analysis, we obtained specific or enhanced 26 binding protein candidates, including PARP1 and NPM, which were localized in nucleus and associated with transcriptional regulation. These results suggest that the induction of SS18-SSX and SS18-SSX binding proteins specific for sphere-forming subpopulation may play important roles of the transcriptional regulation specific for synovial sarcoma initiating cells.

Research Products

• [Journal Article] Analysis of NAB2-STAT6 gene fusion in 17 cases of meningeal solitary fibrous tumor/hemangiopericytoma (2016)
  • Author(s): Yuzawa, S., Nishihara, H., Wang, L., Tsuda, M., Kimura, T., Tanino, M., Tanaka, S.
  • Journal Title: Am J Surg Pathol Volume: Epub ahead of print
  • Peer Reviewed
• [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): Sayaka Yuzawa, Hiroshi Nishihara, Shigeru Yamaguchi, Hiromi Mohri, Lei Wang, Taichi Kimura, Masumi Tsuda, Mishie Tanino, Hiroyuki Kobayashi, Shunsuke Terasaka, Kiyohiro Houkin, Norihiro Sato, Shinya Tanaka
  • Journal Title: Modern Pathology Volume: Epub ahead of print
  • NAID: 120005905622
  • Peer Reviewed
• [Journal Article] Identification and analysis of CXCR4-positive synovial sarcoma initiating cells. (2016)
  • Author(s): Kimura T, Wang L, Tabu K, Tsuda M, Tanino M, Maekawa A, Nishihara H, Hiraga H, Taga T, Oda Y, Tanaka S.
  • Journal Title: Oncogene Volume: 未定 Issue: 30 Pages: 3932-3943
  • DOI: 10.1038/onc.2015.461
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Synthetic PAMPS gel activates BMP/Smad signaling pathway in ATDC5 cells, which plays a significant role in the gel-induced chondrogenic differentiation. (2016)
  • Author(s): Goto K, Kimura T, Kitamura N, Semba S, Ohmiya Y, Aburatani S, Matsukura S, Tsuda M, Kurokawa T, Gong JP, Tanaka S, Yasuda K.
  • Journal Title: J Biomed Mater Res A Volume: 未定 Issue: 3 Pages: 734-746
  • DOI: 10.1002/jbm.a.35615
  • NAID: 120005981343
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A synthetic polymer scaffold reveals the self-maintenance strategies of rat glioma stem cells by organization of the advantageous niche. (2016)
  • Author(s): Tabu K, Muramatsu N, Mangani C, Wu M, Zhang R, Kimura T, Terashima K, Bizen N, Kimura R, Wang W, Murota Y, Kokubu Y, Nobuhisa I, Kagawa T, Kitabayashi I, Bradley M, Taga T.
  • Journal Title: Stem Cells Volume: 34 Issue: 5 Pages: 1151-1162
  • DOI: 10.1002/stem.2299
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] CRK adaptor protein induces epithelial-mesenchymal transition and metastasis of bladder cancer cells via HGF/c-Met feedback loop. (2015)
  • Author(s): Matsumoto R, Tsuda M, Wang L, Maishi N, Abe t, Kimura T, Tanino M, Nishihara H, Hida K, Ohba Y, Shinohara N, Nonomura K, Tanaka S.
  • Journal Title: Cancer Sci Volume: in press Issue: 6 Pages: 709-17
  • DOI: 10.1111/cas.12662
  • Peer Reviewed / Open Access
• [Journal Article] Comprehensive glycomics of a multistep human brain tumor model reveals specific glycosylation patterns related to malignancy. (2015)
  • Author(s): Furukawa J, Tsuda M, Okada K, Kimura T, Piao J, Tanaka S, Shinohara Y.
  • Journal Title: PLoS One Volume: 10 Issue: 7 Pages: e0128300-e0128300
  • DOI: 10.1371/journal.pone.0128300
  • NAID: 120005650133
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Rapid immunohistochemistry based on alternating current electric field for intraoperative diagnosis of brain tumors. (2015)
  • Author(s): Tanino M, Sasajima T, Nanjo H, Akesaka S, Kagaya M, Kimura T, Ishida Y, Oda M, Takahashi M, Sugawara T, Yoshioka T, Nishihara H, Akagami Y, Goto A, Minamiya Y, Tanaka S, R-IHC Study Group.
  • Journal Title: Brain Tumor Pathology Volume: 32 Pages: 20-21
  • NAID: 120005682120
  • Peer Reviewed / Open Access
• [Journal Article] Hydrogen sulfide augments survival signals in warm ischemia and reperfusion of the mouse liver. (2015)
  • Author(s): Shimada, S., Fukai, M., Wakayama, K., Ishikawa, T., Kobayashi, N., Kimura, T., Yamashita, K., Kamiyama, T., Shimamura, T., Taketomi, A., Todo, S.
  • Journal Title: Surgery Today Volume: 45 Issue: 7 Pages: 892-903
  • DOI: 10.1007/s00595-014-1064-4
  • Peer Reviewed / Open Access
• [Journal Article] microRNA 31 functions as an endometrial cancer oncogene by suppressing Hippo tumor suppressor pathway. (2014)
  • Author(s): Mitamura T, Watari H, Wang L, Kanno H, Kitagawa M, Hassan MK, Kimura T, Tanino M, Nishihara H, Tanaka S, Sakuragi N.
  • Journal Title: Molecular Cancer Volume: 13 Issue: 1 Pages: 97-97
  • DOI: 10.1186/1476-4598-13-97
  • NAID: 120005464724
  • Peer Reviewed / Open Access
• [Journal Article] Immunohistochemical evaluation of O6-methylguanine DNA methyltransferase (MGMT) expression in 117 cases of glioblastoma. (2014)
  • Author(s): Miyazaki M, Nishihara H, Terasaka S, Kobayashi H, Yamaguchi S, Ito T, Kamoshima Y, Fujimoto S, Kaneko S, Katoh M, Ishii N, Mohri H, Kimura T, Tanino M, Tanaka S
  • Journal Title: Neuropathology Volume: 7 Issue: 3 Pages: 268-276
  • DOI: 10.1111/neup.12091
  • Peer Reviewed / Open Access
• [Journal Article] Epiregulin enhances tumorigenicity by activating the ERK/MAPK pathway in glioblastoma. (2014)
  • Author(s): Kohsaka S, Hinohara K, Wang L, Nishimura T, Urushido M, Yachi K, Tsuda M, Tanino M, Kimura T, Nishihara H, Gotoh N, Tanaka S.
  • Journal Title: Neuro Oncology Volume: 16 Pages: 960-970
  • Peer Reviewed / Open Access
• [Journal Article] TRIM29 as a novel prostate basal cell marker for diagnosis of prostate cancer (2014)
  • Author(s): Kanno, Y., Watanabe, M., Kimura, T., Nonomura, K., Tanaka, S. and Hatakeyama, S
  • Journal Title: Acta Histochem Volume: 116 Issue: 5 Pages: 708-712
  • DOI: 10.1016/j.acthis.2013.12.009
  • NAID: 120005472205
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] SS18-SSX-regulated miR-17 promotes tumor growth of synovial sarcoma by inhibiting p21WAF1/CIP1. (2014)
  • Author(s): Minami, Y., Kohsaka, S., Tsuda, M., Yachi, K., Hatori, N., Tanino, M., Kimura, T., Nishihara, H., Minami, A., Iwasaki, N., Tanaka, S.
  • Journal Title: Cancer Sci. Volume: 105 Issue: 9 Pages: 1152-1159
  • DOI: 10.1111/cas.12479
  • NAID: 120005515315
  • Peer Reviewed / Open Access
• [Journal Article] Expression of CD163 prevents apoptosis through the production of granulocyte colony-stimulating factor in meningioma (2013)
  • Author(s): Kanno H, Nishihara H, Wang L, Yuzawa S, Kobayashi H, Tsuda M, Kimura T, Tanino M, Terasaka S, Tanaka S
  • Journal Title: Neuro-Oncology Volume: 15 Issue: 7 Pages: 853-64
  • DOI: 10.1093/neuonc/not028
  • Peer Reviewed
• [Journal Article] Downregulation of miRNA-31 induces taxane resistance in ovarian cancer cells through increase of receptor tyrosine kinase MET (2013)
  • Author(s): Takashi Mitamura
  • Journal Title: Oncogenesis Volume: 2 Issue: 3 Pages: e40-e40
  • DOI: 10.1038/oncsis.2013.3
  • Peer Reviewed
• [Journal Article] Inhibition of GSH synthesis potentiates temozolomide-induced bystander effect in glioblastoma. (2013)
  • Author(s): Kohsaka, S.
  • Journal Title: Cancer Letter Volume: 33 Issue: 1 Pages: 68-75
  • DOI: 10.1016/j.canlet.2012.12.005
  • Peer Reviewed
• [Journal Article] Clinicopathological evaluation of cyclooxygenase-2 expression in meningioma: immunohistochemical analysis of 76 cases of low and high-grade meningioma. (2013)
  • Author(s): Kato, Y., Nishihara, H., Mohri, H., Kanno, H., Kobayashi, H., Kimura, T., Tanino, M., Terasaka, S., and Tanaka, S.
  • Journal Title: Brain Tumor Pathol. Volume: 31 Issue: 1 Pages: 23-30
  • DOI: 10.1007/s10014-012-0127-8
  • NAID: 120005537451
  • Peer Reviewed
• [Journal Article] Immunohistochemical molecular expression profile of metastatic brain tumor for potent personalized medicine. (2012)
  • Author(s): Kato Y, Nishihara H, Yuzawa S, Mohri H, Kanno H, Hatanaka Y, Kimura T, Tanino M, Tanaka S.
  • Journal Title: Brain Tumor Pathol Volume: 印刷中 Issue: 3 Pages: 167-174
  • DOI: 10.1007/s10014-012-0124-y
  • NAID: 120005460237
  • Peer Reviewed
• [Presentation] NGS-based MSK-IMPACT analysis reveals specific genetic alterations in recurrent glioblastoma. (2015)
  • Author(s): 35)津田真寿美、高阪真路、王磊、木村太一、谷野美智枝、西原広史、Marc Ladanyi、田中伸哉
  • Organizer: 第74回日本癌学会総会
  • Place of Presentation: 名古屋国際会議場（愛知県・名古屋市）
  • Year and Date: 2015-10-08
• [Presentation] 悪性脳腫瘍におけるチロシンキナーゼ阻害剤への耐性獲得に関与するMSX1の解析 (2015)
  • Author(s): 25)鈴鹿 淳、津田 真寿美、王 磊、谷野 美智枝、木村 太一、西原 広史、田中伸哉
  • Organizer: 平成２７年度 新学術領域研究「がん研究分野の特性等を踏まえた支援活動」がん若手研究者ワークショップ
  • Place of Presentation: 蓼科グランドホテル滝の湯（長野県・茅野市）
  • Year and Date: 2015-09-02
• [Presentation] 膠芽腫における分子標的阻害薬耐性獲得責任分子としてのIGFBP2の同定 (2015)
  • Author(s): 12)津田真寿美、王磊、谷野美智枝、木村太一、西原広史、田中伸哉
  • Organizer: 第33回日本脳腫瘍病理学会
  • Place of Presentation: JRホテルクレメント高松（香川県・高松市）
  • Year and Date: 2015-05-29
• [Presentation] 血管周皮腫・孤在性線維性腫瘍のFFPE検体を用いたNAB2-STAT6融合遺伝子の検出 (2015)
  • Author(s): 5)湯澤 明夏、西原 広史、加藤 容崇、王 磊、木村 太一、津田 真寿美、谷野 美智枝、田中 伸哉
  • Organizer: 第104回日本病理学会総会
  • Place of Presentation: 名古屋国際会議場（愛知県・名古屋市）
  • Year and Date: 2015-04-30
• [Presentation] Gastritis cystica profundaを背景にした重複胃癌の免疫組織学的検討 (2015)
  • Author(s): 6)杢里香、志藤茜、湯澤明夏、石川麻倫、石田雄介、加藤容崇、木村太一、谷野美智枝、西原広史、田中伸哉
  • Organizer: 第104回日本病理学会総会
  • Place of Presentation: 名古屋国際会議場（愛知県・名古屋市）
  • Year and Date: 2015-04-30
• [Presentation] 滑膜肉腫幹細胞の同定と解析 (2014)
  • Author(s): 木村太一
  • Organizer: 第79回インターフェロン・サイトカイン学会
  • Place of Presentation: 北大医学部フラテ（北海道・札幌市）
  • Year and Date: 2014-06-19 – 2014-06-20
• [Presentation] 滑膜肉腫幹細胞の同定と解析 (2013)
  • Author(s): 木村太一, 王磊, 谷野美智枝, 西原広史, 田中伸哉
  • 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] 頭頸部扁平上皮癌におけるNotch1の役割 (2013)
  • Author(s): 稲村直哉, 木村太一, 王磊, 津田真寿美, 谷野美智枝, 西原広史, 福田諭, 田中伸哉
  • 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] 軟部肉腫におけるシグナル伝達系の異常と治療への応用：滑膜肉腫をモデルにして. (2013)
  • Author(s): 田中伸哉、木村太一、津田真寿美、王磊、仙葉慎吾、谷野美智枝、平賀博明、大場雄介、西原広史
  • Organizer: 第102回日本病理学会総会
  • Place of Presentation: ロイトン札幌, 札幌