Adaptation of the most suitable anticancer drug by utilizing new developed three-dimensional model mimicked human tumor microenvironment.

• Project/Area Number: 20790295
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Experimental pathology
• Research Institution: Hokkaido University
• Principal Investigator: TSUDA Masumi Hokkaido University, 大学院・医学研究科, 助教 (30431307)
• Project Period (FY): 2008 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2009: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 腫瘍微小環境 / 抗がん剤 / 腫瘍血管新生 / 腫瘍間質 / 腫瘍環境 / 治療標的分子

Research Abstract

We identify receptor activator of nuclear factor κB ligand (RANKL) as a microenvironment-specific factor essential for tumorigenesis in vivo, utilizing oral squamous cell carcinoma as a model. In addition, in human synovial sarcoma that frequently occurs pulmonary metastasis, the interaction between the tumor and endothelial cells is important for tumor angiogenesis. Src family kinase inhibitor impaired this angiogenesis effectively.

Research Products

• [Journal Article] The adaptor protein Crk induces Src-dependent activation of p38 MAPK in regulation of synovial sarcoma cell proliferation. (2009)
  • Author(s): T.Watanabe, †M.Tsuda, S.Tanaka, Y.Ohba, H.Kawaguchi, T.Majima, H.Sawa, A.Minami
  • Journal Title: Mol.Cancer Res. 7(9) Pages: 1582-92
  • Peer Reviewed
• [Journal Article] Crk adaptor protein induced-phosphorylation of Gab1 on tyrosine 307 via Src is important for organization of focal adhesions and enhanced cell migration. (2009)
  • Author(s): T.Watanabe, M.Tsuda, Y.Makino, T.Konstantinou, H.Nishihara, T.Majima, A.Minami, S.Feller, S.Tanaka
  • Journal Title: Cell Res. 19(5) Pages: 638-650
  • Peer Reviewed
• [Journal Article] Integral role of transcription factor 8 in the negative regulation of tumor angiogenesis. (2009)
  • Author(s): T.Inuzuka, M.Tsuda, H.Kawaguchi, Y.Higashi, Y.Ohba
  • Journal Title: Cancer Res. 69(4) Pages: 1678-1684
  • NAID: 120005367446
  • Peer Reviewed
• [Journal Article] Crk adaptor protein induced-phosphorylation of Gabl on tyrosine 307 via Srcis important for organization of focal adhesions and enhanced cell migration (2009)
  • Author(s): T.Watanabe, M.Tsuda, Y.Makino, T.Konstantinou, H.Nishihara, T.Majima, A.Minami, SM.Feller, S.Tanaka
  • Journal Title: Cell Res. 19 Pages: 638-650
  • Peer Reviewed
• [Journal Article] The adaptor protein Crk induces Src-dependent activation of p38 MAPK in regulation of synovial sarcoma cell proliferation (2009)
  • Author(s): T.Watanabe, M.Tsuda, S.Tanaka, Y.Ohba, H.Kawaguchi, T.Majima, H.Sawa, A.Minami
  • Journal Title: Mol.Cancer Res. 7 Pages: 1582-1592
  • Peer Reviewed
• [Journal Article] Visualization of Ras-PI3K interaction in the endosome using BiFC (2009)
  • Author(s): K.Tsutsumi, Y.Fujioka, M.Tsuda, H.Kawaguchi, Y.Ohba
  • Journal Title: Cell Signal 21 Pages: 1672-1679
  • NAID: 120005367445
  • Peer Reviewed
• [Journal Article] Increased motility and invasiveness of tumor cells that survived 10 Gyirradiation (2009)
  • Author(s): K.Tsutsumi, M.Tsuda, N.Yazawa, H.Nakamura, S.Ishihara, H.Haga, M.Yasuda, R.Yamazaki, H.Shirato, H.Kawaguchi, T.Nishioka, Y.Ohba.
  • Journal Title: Cell Struct.Funct. 34 Pages: 89-96
  • NAID: 40017160767
  • Peer Reviewed
• [Journal Article] Human synovial sarcoma proto-oncogene Syt is essential for early embryonic development through the regulation of cell migration (2009)
  • Author(s): T.Kimura, M.Sakai, K.Tabu, L.Wang, R.Tsunematsu, M.Tsuda, H.Sawa, K.Nagashima, H.Nishihara, S.Hatakeyama, K.Nakayama, M.Ladanyi, S.Tanaka, KI.Nakayama
  • Journal Title: Cell Res. 19 Pages: 638-650
  • Peer Reviewed
• [Journal Article] Integral role of TCF8 in the negative regulation of 4umor angiogenesis (2009)
  • Author(s): Inuzuka T, Tsuda M, Kawaguchi H, Higashi Y, Ohba Y
  • Journal Title: Cancer Res 69 Pages: 1678-1684
  • Peer Reviewed
• [Journal Article] Transcription factor 8 activates R-Ras to regulate angiogenesis (2008)
  • Author(s): Inuzuka T, Tsuda M, Kawaguchi H, Ohba Y
  • Journal Title: Biochem. Biophys. Res. Commun 379 Pages: 510-513
  • NAID: 120005367447
  • Peer Reviewed
• [Journal Article] 細胞内シグナル伝達の可視化とその創薬への応用 (2008)
  • Author(s): 大場雄介、津田真寿美
  • Journal Title: 実験医学 26 Pages: 206-213
• [Presentation] RANKI expression induced by the tumor microenvironment promotes epithelial mesenchymal transition and tumor progression in vivo (2010)
  • Author(s): 山田珠希、津田真寿美、川口秀明、戸塚靖則、進藤正信、大場雄介
  • Organizer: The 8th AACR-JCA Joint Conference
  • Place of Presentation: Hilton Waikoloa Village, HI, (USA)
  • Year and Date: 2010-02-08
• [Presentation] A novel FRET-based biosensor for the measurement of BCR-ABL activity and its response to molecular target drugs in living chronic myeloid leukemia cells (2010)
  • Author(s): T.Mizutani, T.Kondo, S.Darmanine, M.Tsuda, S.Tanaka, M.Asaka, Y.Ohba
  • Organizer: The 8th AACR-JCA Joint Conference
  • Place of Presentation: Hilton Waikoloa Village, HI, (USA)
  • Year and Date: 2010-02-06
• [Presentation] RANKL expression induced by the tumor microenvironment promotes epithelial mesenchymal transition and tumor progression in vivo (2010)
  • Author(s): Yamada T, Tsuda M, Kawaguchi H, Totsuka Y, Shindoh M, Ohba Y
  • Organizer: The 8th Joint Conference of the American Association for Cancer Research and the Japanese Cancer Association
  • Place of Presentation: Hawaii, USA
• [Presentation] Ras-PI3K signaling regulates influenza virus infection (2009)
  • Author(s): Y.Fujioka, M.Tsuda, T.Hattori, J.Sasaki, H.Kawaguchi, T.Sasaki, T.Miyazaki, Y.Ohba
  • Organizer: 第32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: 2009-12-11
• [Presentation] Effect of Src family kinase inhibitor on proliferation and invasion in human synovial sarcoma in vivo (2009)
  • Author(s): R.Arai, M.Tsuda, T.Watanabe, H.Kawaguchi, A.Minami, Y.Ohba
  • Organizer: 第32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: 2009-12-09
• [Presentation] Angiotensin II AT2 receptor antagonizes AT1 receptor-derived signaling via PKC activity in the signaling endosome (2009)
  • Author(s): 津田真寿美, 犬塚貴之, 大場雄介, 川口秀明
  • Organizer: The 26^<th> Annual Meeting of International Society for Heart research Japanese Section
  • Place of Presentation: 北海道大学学術交流会館(札幌市)
  • Year and Date: 2009-12-05
• [Presentation] A FRET-based biosensor for the evaluation of the efficacy of molecular targeted drugs for chronic myeloid leukemia (2009)
  • Author(s): T.Mizutani, T.Kondo, S.Darmanin, N.Tsuda, S.Tanaka, M.Asaka, Y.Ohba
  • Organizer: 第68回日本癌学会総会
  • Place of Presentation: パシフィコ横浜(横浜市)
  • Year and Date: 2009-10-03
• [Presentation] Requirement for tumor microenvironment-induced RANKL expression in the tumorigenesis in vivo (2009)
  • Author(s): 山田珠希、津田真寿美、戸塚靖則、進藤正信、大場雄介
  • Organizer: 第68回日本癌学会総会
  • Place of Presentation: パシフィコ横浜(横浜市)
  • Year and Date: 2009-10-01
• [Presentation] Selective attenuation of angiotensin type 1 receptor signaling by type 2 receptor via PKC in the signaling endosome (2009)
  • Author(s): 津田真寿美, 大場雄介, 川口秀明
  • Organizer: 第32回心筋代謝研究会
  • Place of Presentation: 千里ライフサイエンスセンター(大阪)
  • Year and Date: 2009-07-04
• [Presentation] エンドゾームにおけるRas依存性PI3K活性化機構の時空間的解析 (2009)
  • Author(s): 藤岡容一朗, 堤香織, 津田真寿美, 川口秀明, 大場雄介
  • Organizer: 第61回日本細胞生物学会
  • Place of Presentation: 名古屋国際会議場(名古屋市)
  • Year and Date: 2009-06-04
• [Presentation] Crkが制御するSrcを介したGab1 Y307のリン酸化は、細胞接着斑の形成と運動能の亢進に重要である (2009)
  • Author(s): 津田真寿美、渡部琢哉、牧野吉倫、川口秀明、田中伸哉、大場雄介
  • Organizer: 第61回日本細胞生物学会
  • Place of Presentation: 名古屋国際会議場(名古屋市)
  • Year and Date: 2009-06-02
• [Presentation] Receptor activator of NF-KB ligand(RANKL)発現口腔癌細胞株の悪性形質に関する機能解析 (2009)
  • Author(s): 山田珠希、津田真寿美、川口秀明、戸塚靖則、進藤正信、大場雄介
  • Organizer: 第98回日本病理学会総会
  • Place of Presentation: 国立京都国際会館(京都市)
  • Year and Date: 2009-05-03
• [Presentation] TCF8は血管新生の負の制御因子である (2009)
  • Author(s): 犬塚貴之, 津田真寿美, 田中伸哉, 川口秀明, 東雄二郎, 大場雄介
  • Organizer: 第98回日本病理学会総会
  • Place of Presentation: 国立京都国際会館(京都市)
  • Year and Date: 2009-05-03
• [Presentation] 慢性骨髄性白血病に対する分子標的治療薬の新たな薬効評価系の構築 (2009)
  • Author(s): 水谷龍明, 近藤健, S.Darmanin, 津田真寿美, 甲斐原拓真, 川口秀明, 浅香正博, 大場雄介
  • Organizer: 第98回日本病理学会総会
  • Place of Presentation: 国立京都国際会館(京都市)
  • Year and Date: 2009-05-01
• [Presentation] Effect of Src family kinase inhibitor on proliferation and invasion in human synovial sarcoma in vivo. (2009)
  • Author(s): Arai R, Tsuda M, Watanabe T, Kawaguchi H, Minami A, Ohba Y
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] Requirement for tumor microenvironment-induced RANKL expression in the tumororigenesis in vivo. (2009)
  • Author(s): Yamada T, Tsuda M, Totsuka Y, Shindoh M, Ohba, Y
  • Organizer: 第68回日本癌学会総会
  • Place of Presentation: 横浜
• [Presentation] Development of synovial sarcoma-like tumors in SYT-SSX1 transgenic p53 mutant mice. (2008)
  • Author(s): Tsuda M, Watanabe T, Ohba Y, Tanaka S
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] Visualization of an interaction between Ras and Ras-binding domain in living cells by biomolecular fluorescence complementation (2008)
  • Author(s): Tsutsumi K, Tsuda M, Kawaguchi H, Ohba Y
  • Organizer: The American Society for Biochemistry and Molecular Biology (ASBMB), 2008 Annual Meeting
  • Place of Presentation: San Diego, CA, USA, San Diego Convention Center
• [Presentation] 口腔癌細胞における上皮細胞増殖因子受容体(EGFR)依存的なPTHrP発現制御と局所浸潤能との関連性 (2008)
  • Author(s): 山田珠希、津田真寿美、大場雄介、戸塚靖則、進藤正信、川口秀明
  • Organizer: 第12回日本適応医学会
  • Place of Presentation: 別府、別府市ビーコンプラザ
• [Presentation] 上皮細胞増殖因子(EGF)依存的なPTHrPの発現制御と口腔癌細胞の増殖能・局所浸潤能との関連性 (2008)
  • Author(s): 山田珠希、津田真寿美、大場雄介、川口秀明、戸塚靖則、進藤正信
  • Organizer: 第73回日本インターフェロン・サイトカイン学会学術集会
  • Place of Presentation: 札幌、北海道大学学術交流会館
• [Presentation] 血管新生を制御する新規遺伝子の同定とその機能解析 (2008)
  • Author(s): 犬塚貴之、津田真寿美、田中伸哉、川口秀明、東雄二郎、大場雄介
  • Organizer: 第73回日本インターフェロン・サイトカイン学会学術集会
  • Place of Presentation: 札幌、北海道大学学術交流会館
• [Presentation] Negative regulation of angiogenesis by a zinc-finger transcription factor (2008)
  • Author(s): Inuzuka T, Tsuda M, Tanaka S, Ohba Y
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋、名古屋国際会議場
• [Presentation] Development of synovial sarcoma-like tumors in SYT-SST1 transgenic p53 mutant mice (2008)
  • Author(s): Tsuda M, Watanabe T, Ohba Y, Ta naka S
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋、名古屋国際会議場
• [Presentation] エンドソームにおけるRas依存性PI3K活性化機構のイメージング手法を用いた解析 (2008)
  • Author(s): 藤岡容一朗、堤香織、津田真寿美、川口秀明、大場雄介
  • Organizer: 第31回日本分子生物学会年会
  • Place of Presentation: 神戸、神戸ポートアイランド
• [Presentation] TCF8は血管新生の負の制御因子である。 (2008)
  • Author(s): 犬塚貴之、津田真寿美、田中伸哉、川口秀明、東雄二郎、大場雄介
  • Organizer: 第31回日本分子生物学会年会
  • Place of Presentation: 神戸、神戸ポートアイランド
• [Presentation] 口腔癌細胞の接着に関連する分子の機能解析 (2008)
  • Author(s): 山田珠希、津田真寿美、大場雄介、川口秀明、戸塚靖則、進藤正信
  • Organizer: 第31回日本分子生物学会年会
  • Place of Presentation: 神戸、神戸ポートアイランド
• [Presentation] 慢性骨髄性白血病に対する分子標的治療薬の新たな薬効評価系の構築 (2008)
  • Author(s): 水谷龍明、近藤健、ステファニー ダルマニン、津田真寿美、甲斐原拓真、川口秀明、浅香正博、大場雄介
  • Organizer: 第31回日本分子生物学会年会
  • Place of Presentation: 神戸、神戸ポートアイランド
• [Remarks]
  • URL: http://www.med.hokudai.ac.jp/~clilab-w/
• [Remarks]
  • URL: http://www.med.hokudai.ac.jp/~clilab-w/