Role of cell environmental signaling in the establishment of hematopoietic malignancies

• Project/Area Number: 19390258
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: University of Tsukuba
• Principal Investigator: CHIBA Shigeru University of Tsukuba, 大学院・人間総合科学研究科, 教授 (60212049)
• Co-Investigator(Kenkyū-buntansha): SAKATA Mamiko 筑波大学, 大学院・人間総合科学研究科, 講師 (80451805) ; 熊野 恵城 東京大学, 医学部附属病院, 助教 (90396721)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000); Fiscal Year 2008: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000); Fiscal Year 2007: ¥9,880,000 (Direct Cost: ¥7,600,000、Indirect Cost: ¥2,280,000)
• Keywords: 造血器腫瘍 / 白血病 / 血管新生 / Notch / 遺伝子 / 細胞環境 / 遺伝子異常 / Hes

Research Abstract

癌などの悪性腫瘍は、正常細胞内で遺伝子異常が生じて腫瘍細胞に変化し増殖していく。さらに、腫瘍の周辺には腫瘍細胞が増殖しやすい環境が整っていく。このような腫瘍細胞環境に、細胞内情報伝達システムの一つであるNotchがどのような役割を果たすか調べた。Notch情報伝達の阻害剤により、腫瘍細胞内の情報が遮断されて腫瘍細胞が死にやすくなると同時に、腫瘍に栄養を与える血管新生がうまくできず、細胞環境の面からも腫瘍増殖が抑制されることがわかった。

Research Products

• [Journal Article] Jagged1 suppresses collagen-induced arthritis by indirectly providing a negative signal in CD8+ T cells. (2009)
  • Author(s): Kijima M, Iwata A, Maekawa Y, Uehara H, Izumi K, Kitamura A, Yagita H, Chiba S, Shiota H, Yasutomo K.
  • Journal Title: J Immunol 182(6) Pages: 3566-3572
  • Peer Reviewed
• [Journal Article] Notch signaling confers antigen-presenting cell functions on mast cells (2009)
  • Author(s): Nakano N, Nishiyama C, Yagita H, Koyanagi A, Akiba H, Chiba S, Ogawa H, Okumura K.
  • Journal Title: J Allergy Clin Immunol 123(1) Pages: 74-81
  • Peer Reviewed
• [Journal Article] Notch Activation Induces the Generation of Functional NK Cells from Human Cord Blood CD34-Positive Cells Devoid of IL-15 (2009)
  • Author(s): 原口京子、他
  • Journal Title: Journal of Immunology 192 Pages: 6168-6178
  • Peer Reviewed
• [Journal Article] Notch 2 integrates signaling by the transcription factors RBP-J and CREB1 to promote T cell cytotoxicity (2008)
  • Author(s): Maekawa Y, Minato Y, Ishifune C, Kurihara T, Kitamura A, Kojima H, Yagita H, Sakata-Yanagimoto S, Saito T, Taniuchi I, Chiba S, Sone S, Yasutomo K
  • Journal Title: Nat Immunol 9(10) Pages: 1140-1147
  • Peer Reviewed
• [Journal Article] Evi-1 is a critical regulator for hematopoietic stem cells and transformed leukemic cells (2008)
  • Author(s): Goyama S, Yamamoto G, Sato T, Ichikawa M, Ogawa S, Chiba S, Kurokawa M.
  • Journal Title: Cell Stem Cell 3(2) Pages: 207-220
  • Peer Reviewed
• [Journal Article] Coordinated regulation of transcription factors through Notch2 is an important mediator of mast cell fate (2008)
  • Author(s): Sakata-Yanagimoto M, Nakagami- Yamaguchi E, Saito T, Kumano K, Yasutomo K, Ogawa S, Kurokawa M, Chiba S.
  • Journal Title: Proc Natl Acad Sci USA 105(22) Pages: 7839-7844
  • NAID: 120007138253
  • Peer Reviewed
• [Journal Article] AML1-Evi-1 specifically transforms hematopoietic stem cells through fusion of the entire Evi-1 sequence to AML1 (2008)
  • Author(s): Takeshita M, Ichikawa M, Nitta E, Goyama S, Asai T, Ogawa S, Chiba S, Kurokawa M.
  • Journal Title: Leukemia 22(6) Pages: 1241-1249
  • Peer Reviewed
• [Journal Article] Dendritic cell-mediated NK cell activation is controlled by Jagged2-Notch interaction (2008)
  • Author(s): Kijima M, Yamaguchi T, Ishifune C, Maekawa Y, Koyanagi A, Yagita H, Chiba S, Kishihara K, Shimada M, Yasutomo K.
  • Journal Title: Proc Natl Acad Sci USA 105(19) Pages: 7010-7015
  • Peer Reviewed
• [Journal Article] Fbxw7 acts as a critical fail-safe against premature loss of hematopoietic stem cells and development of T-ALL (2008)
  • Author(s): 8. Matsuoka S, Oike Y, Onoyama I, Iwama A, Arai F, Takubo K, Mashimo Y, Oguro H, Nitta E, Ito K, Miyamoto K, Yoshiwara H, Hosokawa K, Nakamura Y, Gomei Y, Iwasaki H, Hayashi Y, Matsuzaki Y, Nakayama K, Ikeda Y, Hata A, Chiba S, Nakayama KI, Suda T.
  • Journal Title: Genes Dev 22(8) Pages: 986-991
  • Peer Reviewed
• [Journal Article] Regulation Of Notch Signaling By Dynamic Changes In The Precision In S3 Cleavage Of Notch-1. (2008)
  • Author(s): Tagami S, Okochi M, Yanagida K, Ikuta A, Fukumori A, Matsumoto N, Ishizuka-Katsura Y, Nakayama T, Itoh N, Jiang J, Nishitomi K, Kamino K, Morihara T, Hashimoto R, Tanaka T, Kudo T, Chiba S, Takeda M.
  • Journal Title: Mol Cell Biol 28(1) Pages: 165-176
  • Peer Reviewed
• [Journal Article] Fbxw7 acts as a critical fail-safe against premature loss of hematonoietic stem cells and development of T-ALL (2008)
  • Author(s): 松岡佐保子、他
  • Journal Title: Genes & Development 22 Pages: 986-991
  • Peer Reviewed
• [Journal Article] Dendritic cell-mediated NK cell activation is controlled by Jagged2-Notch interaction (2008)
  • Author(s): 木鳩美香、他
  • Journal Title: National Academy of Science, USA 105 Pages: 7010-7015
  • Peer Reviewed
• [Journal Article] Coordinated regulation of transcription factors through Notch2 is an important mediator of mast cell fate (2008)
  • Author(s): 坂田(柳元)麻実子、他
  • Journal Title: National Academy of Science, USA 105 Pages: 7839-7844
  • Peer Reviewed
• [Journal Article] Notch 2 integrates signaling by the transcription factors RBP-J and CREB1 to promote T cell cytotoxicity (2008)
  • Author(s): 前川洋、他
  • Journal Title: Nature Immunology 9 Pages: 1140-1147
  • Peer Reviewed
• [Journal Article] Notch signaling confers antigen-presenting cell functions on mast cells (2008)
  • Author(s): 中野信浩、他
  • Journal Title: Journal of Allergy and Clinical Immunology 123 Pages: 74-81
  • Peer Reviewed
• [Journal Article] Both Notchl and Notch2 contribute to the regulation of melanocyte homeostasis. (2008)
  • Author(s): 熊野 恵城、他
  • Journal Title: Pigment Cell and Melanoma Research 21 Pages: 70-78
  • Peer Reviewed
• [Journal Article] Immunotherapy against metastatic renal cell carcinoma with mature dendritic cells. (2007)
  • Author(s): 松本 明彦、他
  • Journal Title: International Journal of Urology 14 Pages: 277-283
  • Peer Reviewed
• [Journal Article] Expression profiling of immature thymocytes revealed a novel homeobox gene that regulates (2007)
  • Author(s): 河津 正人、他
  • Journal Title: Journal of Immunology 179 Pages: 5335-5345
  • Peer Reviewed
• [Journal Article] Regulation Of Notch Signaling By Dynamic Changes In The Precision In S3 Cleavage Of No (2007)
  • Author(s): 田上 真次、他
  • Journal Title: Molecular and Cellular Biolology 28 Pages: 165-176
  • Peer Reviewed
• [Journal Article] The monolayer formation of Bergmann glial cells is regulated by Notch/RBP-J signaling. (2007)
  • Author(s): Okiru Komine、他
  • Journal Title: Developmental Biolology 311 Pages: 238-250
  • Peer Reviewed
• [Journal Article] JAGGEDl and deltal differentially regulate the outcome of experimental autoimmune encep (2007)
  • Author(s): Wassim Elyaman、他
  • Journal Title: Journal of Immunology 179 Pages: 5990-5998
  • Peer Reviewed
• [Presentation] Notch signaling as a therapeutic target of cancer. (2008)
  • Author(s): Mamiko Sakata-Yanagimoto, Shigeru Chiba, 他
  • Organizer: The 13th Japan-Korea Cancer Research Workshop.
  • Place of Presentation: 韓国Daejeon
  • Year and Date: 2008-12-13
• [Presentation] hairy ellhancer of split-1(Hes-1)による造血前駆細胞の不死化 (2008)
  • Author(s): 中原史雄、他
  • Organizer: 第70回日本血液学会総会
  • Place of Presentation: 京都
  • Year and Date: 2008-10-11
• [Presentation] Gain-of-function mutations and copy number increases of Notch2 in diffuse large B-cell lymphoma (2007)
  • Author(s): Suk-young Lee, Shigeru Chiba, 他
  • Organizer: 49th American Society of Hematology Annual Meeting
  • Place of Presentation: 米国ジョージア州アトランタ
  • Year and Date: 2007-12-10
• [Presentation] Gain-of-Function Mutations and Copy Number Increases of Notch2 in Diffuse Large B-Cell Lymphoma (2007)
  • Author(s): 李碩瑛、千葉 滋、他
  • Organizer: 第49回米国血液学会
  • Place of Presentation: 米国(アトランタ)
  • Year and Date: 2007-12-10
• [Presentation] Essential role of Notch signaling in in vivo mucosal-type mast cell maturation and localization, and eradication of parasites (2007)
  • Author(s): Mamiko Sakata-Yanagimoto, Shigeru Chiba, 他
  • Organizer: 第37回日本免疫学会総会・学術集会
  • Place of Presentation: 東京
  • Year and Date: 2007-11-21
• [Presentation] 分子標的としてのNotchシグナル (2007)
  • Author(s): 千葉 滋
  • Organizer: 第69回日本血液学会・第49回日本臨床血液学合同総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-12
• [Presentation] Activating mutations and copy number gains of Notch2 in diffuse large B-cell lymphoma (2007)
  • Author(s): Suk-young Lee, Shigeru Chiba, 他
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-05
• [Book] 造血器腫瘍アトラス-形態、免疫、染色体と遺伝子- 改訂第4版, 「Notch遺伝子」 (2009)
  • Author(s): 千葉滋
  • Publisher: 日本医事新報社
• [Book] Annual Review血液2008, 「Notch遺伝子と造血幹細胞増幅および白血病との関わり」 (2008)
  • Author(s): 千葉滋
  • Publisher: 中外医学社
• [Patent(Industrial Property Rights)] ヒトDelta1とヒト免疫グロブリンGのFc部分との融合タンパク質を産生する形質転換体 (2007)
  • Inventor(s): 千葉滋、安友康二
  • Industrial Property Rights Holder: 徳島大学
  • Industrial Property Number: 2007-318431
  • Filing Date: 2007-12-10