ＴＧＦ－βファミリーのがん微小環境に及ぼす作用とがん治療戦略

• Project Area: Integrative Research on Cancer Microenvironment Network
• Project/Area Number: 22112002
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Research Institution: The University of Tokyo
• Principal Investigator: 宮園 浩平 The University of Tokyo, 医学(系)研究科(研究院), 教授 (90209908)
• Co-Investigator(Kenkyū-buntansha): 城 潤一郎 独立行政法人放射線医学総合研究所, その他部局等, 研究員 (60511243) ; 田畑 泰彦 京都大学, 再生医科学研究所, 教授 (50211371)
• Project Fiscal Year: 2010-06-23 – 2015-03-31(Estimated)
• Project Status: Completed(Fiscal Year 2014)
• Budget Amount: ¥433,420,000 (Direct Cost : ¥333,400,000、Indirect Cost : ¥100,020,000); Fiscal Year 2014 : ¥80,730,000 (Direct Cost : ¥62,100,000、Indirect Cost : ¥18,630,000); Fiscal Year 2013 : ¥82,290,000 (Direct Cost : ¥63,300,000、Indirect Cost : ¥18,990,000); Fiscal Year 2012 : ¥88,400,000 (Direct Cost : ¥68,000,000、Indirect Cost : ¥20,400,000); Fiscal Year 2011 : ¥87,490,000 (Direct Cost : ¥67,300,000、Indirect Cost : ¥20,190,000); Fiscal Year 2010 : ¥94,510,000 (Direct Cost : ¥72,700,000、Indirect Cost : ¥21,810,000)
• Keywords: がん微小環境 / シグナル伝達 / 生体材料 / 生体イメージング / ゲノム科学 / 微小環境 / がん浸潤 / 転移 / 血管新生 / リンパ管新生 / BMP / TGF-β

Outline of Annual Research Achievements

1)　TGF-βによって誘導されるEMTの制御：肺腺がんの悪性度に関わる転写因子TTF-1のTGF-βシグナルに与える影響を調べ、Smad4を介しない、TTF-1/Smad3複合体の標的遺伝子としてLMO3を同定した。TTF-1とTGF-βの共同による新規のシグナル経路が明らかとなった。
２）CAFの誘導とその働きに関する研究：TGF-βとFGFの共同作用で誘導される線維芽細胞は独自の活性化した形質を獲得する。活性化線維芽細胞はIntegrin α3などを特徴的に発現することが明らかとなった。一方、血管内皮細胞もTGF-βによって間葉系細胞に分化するが（EndMT）、EndMTの過程ではFGFは抑制的に作用することが明らかとなった。
３）血管・リンパ管新生の制御に関する研究：BMP-9に加えてPDGFがリンパ管新生に重要な役割を果たすことが明らかとなった。In vitroだけでなく、in vivoでもPDGFRβFcや低分子化合物がリンパ管新生を抑制することを確認した。
４）BMPのがんとがん微小環境に関する研究：本年度の研究の過程でBMP-4が大腸がんの細胞で特異的に高発現していることが明らかとなった。他のBMPの発現は変化なく、BMP-4のみに特異的な現象と考えられた。BMP-4は大腸がん細胞のアポトーシスを抑制することからBMP-4の作用の制御ががんの進展に重要な役割を果たすことが明らかとなった。
５）人工がん微小環境の創成：体内に近い状態で細胞の生物機能を維持させる細胞集合体の培養技術を創製した。集合体内部にゼラチンハイドロゲル微粒子を均一に組み入れ、細胞への栄養、酸素の供給を効率化させた。その結果、細胞生存率と骨芽細胞分化が有意に増加した。ゼラチンハイドロゲル粒子からBMPを徐放することで、より高い効率の骨分化が可能となった。

Current Status of Research Progress

Research has progressed on the whole more than it was originally planned.

Reason

TTF-1とTGF-βのクロストークで制御される標的遺伝子としてLMO3を同定し、全く新しいシグナル制御機構を発見した。研究はおおむね順調に進行し、本研究の成果としてPNASなどに9編の論文を発表した。またBMP-4の大腸がんにおける重要な役割を見出したため、研究費の繰り越し申請を行い、平成26年9月までに成果をとりまとめた。

Research Output

• [Journal Article] Widespread inference of weighted microRNA-mediated gene regulation in cancer transcriptome analysis (2013)
  • Author(s): Suzuki HI
  • Journal Title: Nucleic Acids Res Volume : 41 Pages : e62
  • DOI: 10.1093/nar/gks1439
• [Journal Article] p53 actions on microRNA expression and maturation pathway (2013)
  • Author(s): Suzuki HI
  • Journal Title: Methods Mol Biol Volume : 962 Pages : 165-181
  • DOI: 10.1007/978-1-62703-236-0_14
• [Journal Article] Genome-wide mechanisms of Smad binding (2013)
  • Author(s): Morikawa M
  • Journal Title: Oncogene Volume : 32 Pages : 1609-1615
  • DOI: 10.1038/onc.2012.191
• [Journal Article] The COUP-TFII variant lacking a DNA-binding domain inhibits the activation of the Cyp7a1 promoter through physical interaction with COUP-TFII (2013)
  • Author(s): Yamazaki T, Suehiro J, Miyazaki H, Minami T, Kodama T, Miyazono K, Watabe T.
  • Journal Title: Biochemical Journal Volume : 452 Pages : 345-357
  • DOI: 10.1042/BJ20121200
• [Journal Article] Computational dissection of distinct microRNA activity signatures associated with peripheral T cell lymphoma subtypes (2013)
  • Author(s): Suzuki HI, Matsuyama H, Noguchi M, Yao T, Komatsu N, Mano H, Sugimoto K, Miyazono K.
  • Journal Title: Leukemia Volume : 27 Pages : 2107-2111
  • DOI: 10.1038/leu.2013.121
• [Journal Article] Basolateral BMP signaling in polarized epithelial cells (2013)
  • Author(s): Saitoh M, Shirakihara T, Fukasawa A, Horiguchi K, Sakamoto K, Sugiya H, Beppu H, Fujita Y, Morita I, Miyazono K, Miyazawa K.
  • Journal Title: PLoS One Volume : 13 Pages : e62659
  • DOI: 10.1371/journal.pone.0062659
• [Journal Article] Oligodendrocyte transcription factor 1 (Olig1) is a Smad cofactor involved in cell motility induced by transforming growth factor-β (2013)
  • Author(s): Motizuki M, Isogaya K, Miyake K, Ikushima H, Kubota T, Miyazono K, Saitoh M, Miyazawa K.
  • Journal Title: Journal of Biological Chemistry Volume : 288 Pages : 18911-18922
  • DOI: 10.1074/jbc.M113.480996
• [Journal Article] Bi-directional roles of bone morphogenetic proteins in cancer: another molecular Jekyll and Hyde? (2013)
  • Author(s): Ehata S, Yokoyama Y, Takahashi K, Miyazono K.
  • Journal Title: Pathology International Volume : 63 Pages : 287-296
  • DOI: 10.1111/pin.12067
• [Journal Article] Identification of integrin α3 as a molecular marker of cells undergoing epithelial-mesenchymal transition and of cancer cells with aggressive phenotypes. (2013)
  • Author(s): Shirakihara T, Kawasaki T, Fukagawa A, Semba K, Sakai R, Miyazono K, Miyazawa K, Saitoh M.
  • Journal Title: Cancer Science Volume : 104 Pages : 1189-1197
  • DOI: 10.1111/cas.12220
• [Journal Article] Bone morphogenetic protein-9 inhibits lymphatic vessel formation via activin receptor-like kinase 1 during development and cancer progression (2013)
  • Author(s): Yoshimatsu Y, Lee YG, Akatsu Y, Taguchi L, Suzuki HI, Cunha SI, Maruyama K, Suzuki Y, Yamazaki T, Katsura A, Oh SP, Zimmers TA, Lee SJ, Pietras K, Koh GY, Miyazono K, Watabe T.
  • Journal Title: Proceedings of the National Academy of Sciences of U S A. Volume : 110 Pages : 18940-18945
  • DOI: 10.1073/pnas.1310479110
• [Journal Article] Degree of biological apatite c-axis orientation rather than bone mineral density controls mechanical function in bone regenerated using recombinant bone morphogenetic protein-2 (2013)
  • Author(s): Ishimoto T, Nakano T, Umakoshi Y, Yamamoto M, Tabata Y.
  • Journal Title: Journal of Bone and Mineral Research Volume : 28 Pages : 1170-1179
  • DOI: 10.1002/jbmr.1825
• [Journal Article] Preparation and functional evaluation of cell aggregates incorporating gelatin microspheres with different degradabilities (2013)
  • Author(s): Tajima S, Tabata Y.
  • Journal Title: Journal of Tissue Engineering and Regenerative Medicine Volume : 7 Pages : 801-811
  • DOI: 10.1002/term.1469
• [Journal Article] Structure of a dominant-negative helix-loop-helix transcriptional regulator suggests mechanisms of autoinhibition (2012)
  • Author(s): Ishii R
  • Journal Title: EMBO Journal Volume : 31 Pages : 2541-2552
  • DOI: 10.1038/emboj.2012.77
• [Journal Article] Engineering fibrotic tissue in pancreatic cancer: a novel three-dimensional model to investigate nanoparticle delivery (2012)
  • Author(s): Hosoya H
  • Journal Title: Biochemical and Biophysical Research Communications Volume : 419 Pages : 32-37
  • DOI: 10.1016/j.bbrc.2012.01.117
• [Journal Article] TGF-β-induced epithelial-mesenchymal transition of A549 lung adenocarcinoma cells is enhanced by pro-inflammatory cytokines derived from RAW 264.7 macrophage cells (2012)
  • Author(s): Kawata M
  • Journal Title: Journal of Biochemistry Volume : 151 Pages : 205-216
  • DOI: 10.1093/jb/mvs136
• [Journal Article] TGF-β drives epithelial-mesenchymal transition through δEF1-mediated downregulation of ESRP (2012)
  • Author(s): Horiguchi K
  • Journal Title: Oncogene Volume : 31 Pages : 3190-3201
  • DOI: 10.1038/onc.2011.493
• [Journal Article] TGF-β-induced mesenchymal transition of MS-1 endothelial cells requires Smad-dependent cooperative activation of Rho signals and MRTF-A (2012)
  • Author(s): Mihira H
  • Journal Title: Journal of Biochemistry Volume : 151 Pages : 145-156
  • DOI: 10.1093/jb/mvr121
• [Journal Article] TGF-β signal transduction spreading to a wider field: a broad variety of mechanisms for context-dependent effects of TGF-β (2012)
  • Author(s): Ikushima H
  • Journal Title: Cell & Tissue Research Volume : 347 Pages : 37-49
  • DOI: 10.1007/s00441-011-1179-5
• [Journal Article] Drosophila CORL is required for Smad2-mediated activation of Ecdysone Receptor expression in the mushroom body (2012)
  • Author(s): Takaesu NT
  • Journal Title: Development Volume : 139 Pages : 3392-3401
  • DOI: 10.1242/dev.079442
• [Journal Article] TGF-β-induced apoptosis of B-cell lymphoma Ramos cells through reduction of MS4A1/CD20 (2012)
  • Author(s): Kawabata KC
  • Journal Title: Oncogene Volume : 32 Pages : 2096-2106
  • DOI: 10.1038/onc.2012.219
• [Journal Article] Prostate cancer cells and bone stromal cells mutually interact with each other through bone morphogenetic protein-mediated signals (2012)
  • Author(s): Nishimori H
  • Journal Title: J Biol Chem Volume : 287 Pages : 20037-20046
  • DOI: 10.1074/jbc.M112.353094
• [Journal Article] Coordinated expression of REG4 and aldehyde dehydrogenase 1 regulating tumourigenic capacity of diffuse-type gastric carcinoma-initiating cells is inhibited by TGF-β (2012)
  • Author(s): Katsuno Y
  • Journal Title: J Pathol Volume : 228 Pages : 391-404
  • DOI: 10.1002/path.4020
• [Journal Article] Smad7-deficient mice show growth retardation with reduced viability (2012)
  • Author(s): Tojo M
  • Journal Title: J Biochem Volume : 151 Pages : 621-631
  • DOI: 10.1093/jb/mvs022
• [Journal Article] Tumor-promoting functions of transforming growth factor-β in progression of cancer (2012)
  • Author(s): Miyazono K
  • Journal Title: Ups J Med Sci Volume : 117 Pages : 143-152
  • DOI: 10.3109/03009734.2011.638729
• [Journal Article] Therapeutic effect of local administration of low-dose simvastatin-conjugated gelatin hydrogel for fracture healing (2012)
  • Author(s): Fukui T
  • Journal Title: J Bone Miner Res Volume : 27 Pages : 1118-1131
  • DOI: 10.1002/jbmr.1558
• [Journal Article] Cell type-specific target selection by combinatorial binding of Smad2/3 proteins and hepatocyte nuclear factor 4alpha in HepG2 cells (2011)
  • Author(s): Mizutani A, et al
  • Journal Title: Journal of Biological Chemistry Volume : 286 Pages : 29848-29860
• [Journal Article] TGF-β regulates isoform switching of FGF receptors and epithelial-mesenchymal transition (2011)
  • Author(s): Shirakihara T, et al
  • Journal Title: EMBO Journal Volume : 30 Pages : 783-795
• [Journal Article] Arkadia-beyond the TGF-β pathway (2011)
  • Author(s): Miyazono K, Koinuma D
  • Journal Title: Journal of Biochemistry Volume : 149 Pages : 1-3
• [Journal Article] Autocrine TGF-β protects breast cancer cells from apoptosis through reduction of BH3-only protein, Bim (2011)
  • Author(s): Hoshino Y, et al
  • Journal Title: Journal of Biochemistry Volume : 149 Pages : 55-65
• [Journal Article] Transforming growth factor-β decreases the cancer-initiating cell population within diffuse-type gastric carcinoma cells (2011)
  • Author(s): Ehata S, et al
  • Journal Title: Oncogene Volume : 30 Pages : 783-795
• [Journal Article] Activation of Bmp2-Smad1 signal and its regulation by coordinated alteration of H3K27 trimethylation in Ras-induced senescence (2011)
  • Author(s): Kaneda A
  • Journal Title: PLoS Genetics Volume : 7 Pages : E1002359
  • DOI: 10.1371/journal.pgen.1002359
• [Journal Article] MCPIP1 ribonuclease antagonizes dicer and terminates microRNA biogenesis through precursor microRNA degradation (2011)
  • Author(s): Suzuki HI
  • Journal Title: Molecular Cell Volume : 44 Pages : 424-436
  • DOI: 10.1016/j.molcel.2011.09.012
• [Journal Article] miR-135b mediates NPM-ALK-driven oncogenicity and renders IL-17-producing immunophenotype to anaplastic large cell lymphoma (2011)
  • Author(s): Matsuyama H
  • Journal Title: Blood Volume : 118 Pages : 6881-6892
  • DOI: 10.1182/blood-2011-05-354654
• [Journal Article] Bone morphogenetic protein-2 and -4 play tumor suppressive roles in human diffuse-type gastric carcinoma (2011)
  • Author(s): Shirai YT
  • Journal Title: American Journal of Pathology Volume : 179 Pages : 2920-2930
  • DOI: 10.1016/j.ajpath.2011.08.022
• [Journal Article] Ets family members induce lymphangiogenesis through physical and functional interaction with Prox1 (2011)
  • Author(s): Yoshimatsu Y
  • Journal Title: Journal of Cell Science Volume : 124 Pages : 2753-2762
  • DOI: 10.1242/jcs.083998
• [Journal Article] RB1CC1 protein positively regulates transforming growth factor-beta signaling through the modulation of Arkadia E3 ubiquitin ligase activity (2011)
  • Author(s): Koinuma D
  • Journal Title: Journal of Biological Chemistry Volume : 286 Pages : 32502-32512
  • DOI: 10.1074/jbc.M111.227561
• [Journal Article] ChIP-seq reveals cell type-specific binding patterns of BMP-specific Smads and a novel binding motif (2011)
  • Author(s): Morikawa M
  • Journal Title: Nucleic Acids Research Volume : 39 Pages : 8712-8727
  • DOI: 10.1093/nar/gkr572
• [Journal Article] Synergistic effects of the dual release of stromal cell-derived factor -1 and bone morphogenetic protein-2 from hydrogels on bone regeneration (2011)
  • Author(s): Ratanavaraporn J
  • Journal Title: Biomaterials Volume : 32 Pages : 2797-2811
  • DOI: 10.1016/j.biomaterials.2010.12.052
• [Journal Article] Enhancement of ectopic osteoid formation following the dual release of bone morphogenetic protein-2 and Wnt1 inducible signaling pathway protein 1 from gelatin sponges (2011)
  • Author(s): Kohara H
  • Journal Title: Biomaterials Volume : 32 Pages : 5726-5732
  • DOI: 10.1016/j.biomaterials.2011.04.035
• [Journal Article] Arkadia complexes with clathrin adaptor AP2 and regulates EGF signalling (2010)
  • Author(s): Mizutani A, et al
  • Journal Title: Journal of Biochemistry Volume : 148 Pages : 733-741
• [Journal Article] Smad7 inhibits transforming growth factor-beta family type I receptors through two distinct modes of interaction (2010)
  • Author(s): Kamiya Y, et al
  • Journal Title: Journal of Biological Chemistry Volume : 285 Pages : 30804-30813
• [Journal Article] Exogenous introduction of tissue inhibitor of metalloproteinase 2 reduces accelerated growth of TGF-β-disrupted diffuse-type gastric carcinoma (2010)
  • Author(s): Johansson E, et al
  • Journal Title: Cancer Science Volume : 101 Pages : 2398-2403
• [Journal Article] Identification of a phosphorylation site in c-Ski as serine 515 (2010)
  • Author(s): Nagata M, et al
  • Journal Title: Journal of Biochemistry Volume : 148 Pages : 423-427
• [Journal Article] TGF-beta signalling : a complex web in cancer progression (2010)
  • Author(s): Ikushima H, Miyazono K
  • Journal Title: Nature Reviews Cancer Volume : 10 Pages : 415-424
• [Journal Article] Dynamics of microRNA biogenesis : crosstalk between p53 network and microRNA processing pathway (2010)
  • Author(s): Suzuki HI, Miyazono K
  • Journal Title: Journal of Molecular Medicine Volume : 88 Pages : 1085-1094
• [Journal Article] Mineralization, biodegradation, and drug release behavior of gelatin/apatite composite microspheres for bone regeneration (2010)
  • Author(s): Leeuwenburgh SC, Jo J, et al
  • Journal Title: Biomacromolecules Volume : 11 Pages : 2653-2659
• [Presentation] Genome-wide identification of Smad2/3 binding regions during TGF-beta-induced epithelial to mesenchymal transition in NMuMG cells (2013)
  • Author(s): Tomohiro Ogami
  • Organizer: 9th AACR-JCA Joint Conference
  • Place of Presentation: Hyatt Regency Maui (米国、ハワイ）
  • Year and Date: 20130221-20130225
• [Presentation] BMP-9/ALK-1 signals inhibit proliferation of lymphatic endothelial cells and reprogram them to blood vascular endothelial cells through downregulation of Prox1 expression (2013)
  • Author(s): Yasuhiro Yoshimatsu, Hiroshi I Suzuki
  • Organizer: 9th AACR-JCA Joint Conference
  • Place of Presentation: Hyatt Regency Maui (米国、ハワイ）
  • Year and Date: 20130221-20130225
• [Presentation] TGF-β ファミリーシグナルの分子機構 (2013)
  • Author(s): 宮園浩平
  • Organizer: 第３６回日本分子生物学会年会
  • Place of Presentation: 神戸ポートアイランド（兵庫県神戸市）
  • Year and Date: 2013-12-03 – 2013-12-06
• [Presentation] TGF-beta signals in tumor microenvironment and treatment of cancer (2013)
  • Author(s): Miyazono K.
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜パシフィコ（神奈川県横浜市）
  • Year and Date: 2013-10-03 – 2013-10-05
• [Presentation] BMP-9/ALK1 signals negatively regulate the lymphatic vessel formation in development and cancer by downregulating Prox1 (2013)
  • Author(s): 吉松康裕、Lee YG、赤津裕一、田口瑠奈、鈴木 洋、Cunha SI、鈴木夕佳、山崎智子、桂 彰宏、森下保幸、Oh SP、Zimmers TA、Lee SJ、Pietras K、Koh GY、渡部徹郎、宮園浩平
  • Organizer: 第21回日本血管生物医学会学術集会
  • Place of Presentation: 千里阪急ホテル（大阪府豊中市）
  • Year and Date: 2013-09-26 – 2013-09-28
• [Presentation] リンパ管発生および腫瘍リンパ管新生におけるBMP-9/ALK-1シグナルの役割 (2013)
  • Author(s): 吉松康裕、Lee YG、赤津裕一、田口瑠奈、鈴木 洋、Cunha SI、丸山和一、鈴木夕佳、山崎智子、桂 彰宏、森下保幸、Oh SP、Zimmers TA、Lee SJ、Pietras K、Koh GY、渡部徹郎、宮園浩平
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: 横浜パシフィコ（神奈川県横浜市）
  • Year and Date: 2013-09-11 – 2013-09-13
• [Presentation] TGF-βシグナルとがん (2013)
  • Author(s): 宮園浩平
  • Organizer: 平成25年度 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（長野県茅野市）
  • Year and Date: 2013-09-04 – 2013-09-07
• [Presentation] リンパ管形成におけるBMP-9シグナルの役割 (2013)
  • Author(s): 吉松康裕
  • Organizer: 第3回リンパ学に関する松本カンファランス
  • Place of Presentation: 浅間温泉保養所みやま荘（長野）
  • Year and Date: 2013-08-23 – 2013-08-24
• [Presentation] TGF-β signaling in regulation of cancer stem cells and EMT (2013)
  • Author(s): Miyazono K.
  • Organizer: FASEB Summer Research Conferences on the TGF-β Superfamily
  • Place of Presentation: Steamboat Spring (Colorado, U.S.A.)
  • Year and Date: 2013-07-28 – 2013-08-02
• [Presentation] TGF-βによるがん進展制御 (2013)
  • Author(s): 宮園浩平
  • Organizer: 第22回日本がん転移学会学術集会・総会
  • Place of Presentation: ホテルブエナビスタ（長野県松本市）
  • Year and Date: 2013-07-11 – 2013-07-12
• [Presentation] リンパ管形成におけるBMP-9/ALK-1シグナルの役割 (2013)
  • Author(s): 吉松康裕、赤津裕一、田口瑠奈、鈴木 洋、渡部徹郎、宮園浩平
  • Organizer: 第２０回BMP研究会
  • Place of Presentation: アクトシティ浜松コングレスセンター（静岡県浜松市）
  • Year and Date: 2013-07-05 – 2013-07-05
• [Presentation] TGF-βは小細胞肺がんの進展を抑制する (2013)
  • Author(s): 村井文彦、江幡正悟、宮園浩平
  • Organizer: 第17回日本がん分子標的治療学会学術集会
  • Place of Presentation: 国立京都国際会館（京都府京都市）
  • Year and Date: 2013-06-12 – 2013-06-14
• [Presentation] TGF-βシグナルによるがん幹細胞・微小環境の制御 (2013)
  • Author(s): 宮園浩平
  • Organizer: 第102回日本病理学会総会
  • Place of Presentation: ロイトン札幌（北海道札幌市）
  • Year and Date: 2013-06-06 – 2013-06-08
• [Presentation] EMT and EndMT induced by TGF-β (Keynote Presentation) (2013)
  • Author(s): Miyazono K.
  • Organizer: Transforming Growth Factor Signaling : Anniversary Symposium
  • Place of Presentation: UCSF (San Francisco, U.S.A.)
  • Year and Date: 2013-04-05 – 2013-04-06
• [Presentation] Transforming growth factor (TGF)-beta negatively regulates small cell lung cancer progression (2012)
  • Author(s): Fumihiko Murai
  • Organizer: 第85回日本生化学大会
  • Place of Presentation: 福岡国際会議場（福岡）
  • Year and Date: 20121214-20121216
• [Presentation] Roles of TGF-beta family signals in the proliferation of lymphatic endothelial cells (2012)
  • Author(s): Luna Taguchi
  • Organizer: 第２０回日本血管生物医学会学術集会
  • Place of Presentation: あわぎんホール（徳島）
  • Year and Date: 20121205-20121207
• [Presentation] Roles of TGF-beta family signals in the proliferation of lymphatic endothelial cells derived from mouse ES cells (2012)
  • Author(s): Tomoko Yamazaki
  • Organizer: 第２０回日本血管生物医学会学術集会
  • Place of Presentation: あわぎんホール（徳島）
  • Year and Date: 20121205-20121207
• [Presentation] Biomaterials technology indispensable for regenerative medicine and stem cell biology (2012)
  • Author(s): Yasuhiko Tabata
  • Organizer: World Stem Cell Summit 2012
  • Place of Presentation: Palm Beach County Convention Center (フロリダ、米国）
  • Year and Date: 20121203-20121205
• [Presentation] Tumor promotive and suppressive function of TGF-beta (2012)
  • Author(s): Kohei Miyazono
  • Organizer: 43rd International Symposium of the Princess Takamatsu Cancer Research Fund
  • Place of Presentation: ホテルグランドパレス（東京）
  • Year and Date: 20121114-20121116
• [Presentation] Regulation of cancer initiating cell function by TGF-beta (2012)
  • Author(s): Kohei Miyazono
  • Organizer: 第７１回日本癌学会学術総会
  • Place of Presentation: ロイトン札幌（札幌）
  • Year and Date: 20120919-20120921
• [Presentation] Regulation of Smad3 binding by FoxA1/2 in adenocarcinoma cells (2012)
  • Author(s): Kazunobu Isogaya
  • Organizer: 第７１回日本癌学会学術総会
  • Place of Presentation: ロイトン札幌（札幌）
  • Year and Date: 20120919-20120921
• [Presentation] 腫瘍微小循環の機能的破綻 (2012)
  • Author(s): 宮園 浩平
  • Organizer: 千里ライフサイエンスセミナー「がんの転移・浸潤と微小環境」
  • Place of Presentation: 千里ライフサイエンスセンタービル（大阪府豊中市）
  • Year and Date: 20120224-20120224
• [Presentation] TGF-βシグナルによるがん微小環境ネットワークの制御 (2011)
  • Author(s): 宮園 浩平
  • Organizer: 第70回日本癌学会学術集会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 20111005-20111005
• [Presentation] Autocrine TGF-beta protects breast cancer cells from apoptosis through reduction of BH3-only protein, Bim (2011)
  • Author(s): Hoshino Y
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 国立京都国際会館（京都府京都市）
  • Year and Date: 20110923-20110923
• [Presentation] Ets family members induce lymphangiogenesis through physical and functional interaction with Prox1 (2011)
  • Author(s): 吉松康裕
  • Organizer: 第２回リンパ管に関する松本カンファランス
  • Place of Presentation: 浅間温泉みやま荘（長野県松本市）
  • Year and Date: 20110827-20110827
• [Presentation] リンパ管形成における骨形成因子(BMP)シグナルの役割 (2011)
  • Author(s): 吉松康裕
  • Organizer: 第１８回BMP研究会
  • Place of Presentation: 大阪大学中之島センター（大阪府大阪市）
  • Year and Date: 20110731-20110731
• [Presentation] スキルス胃癌においてBMP-2/4は腫瘍抑制因子として作用する (2011)
  • Author(s): 白井陽太郎
  • Organizer: 第１８回BMP研究会
  • Place of Presentation: 大阪大学中之島センター（大阪府大阪市）
  • Year and Date: 20110731-20110731
• [Presentation] TGF-β signaling and tumor microenvironment (2011)
  • Author(s): Kohei Miyazono
  • Organizer: JSIR-MMCB2011 (Japanese Society of Interferon & Cytokine Research/International Symposium on Molecular Cell Biology of Macrophage)
  • Place of Presentation: ANAゲートタワーホテル大阪（大阪府泉佐野市）
  • Year and Date: 20110520-20110520
• [Presentation] TGF-beta, EMT, and TGF-beta signaling inhibitors in cancer progression (2011)
  • Author(s): Kohei Miyazono
  • Organizer: Keystone symposia : Epithelial plasticity and epithelial to mesenchymal transition
  • Place of Presentation: Fairmont Waterfront(カナダ、バンクーバー)(招待講演)
  • Year and Date: 2011-01-25
• [Presentation] がん細胞とこれを取り巻く細胞・新しいがん治療の試み (2010)
  • Author(s): 宮園浩平
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会・合同年会
  • Place of Presentation: 東京大学安田講堂(東京都文京区)(市民公開講座)(招待講演)
  • Year and Date: 2010-12-11
• [Presentation] Roles of TGF-beta signaling in cancer (2010)
  • Author(s): Kohei Miyazono
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会・合同年会
  • Place of Presentation: 神戸ポートアイランド(兵庫県神戸市)(大会長企画シンポジウム)(招待講演)
  • Year and Date: 2010-12-09
• [Presentation] Ets family members induce lymphangiogenesis via physical and functional interaction with Prox1 (2010)
  • Author(s): 吉松康裕、三平元、宮園浩平、渡部徹郎, 他
  • Organizer: 第18回日本血管生物医学会学術集会
  • Place of Presentation: 梅田スカイビル(大阪府大阪市)
  • Year and Date: 2010-12-02
• [Presentation] Analysis of VEGFR2 signaling for endothelial differentiation of embryonic stem cell-derived VEGFR2+cells (2010)
  • Author(s): 佐瀬仁志、渡部徹郎、宮園浩平, 他
  • Organizer: 第18回日本血管生物医学会学術集会
  • Place of Presentation: 梅田スカイビル(大阪府大阪市)
  • Year and Date: 2010-12-01
• [Presentation] Identification of novel COUP-TFII isoform in blood vascular and lymphatic endothelial cells (2010)
  • Author(s): 山崎智子、渡部徹郎、宮園浩平, 他
  • Organizer: 第18回日本血管生物医学会学術集会
  • Place of Presentation: 梅田スカイビル(大阪府大阪市)
  • Year and Date: 2010-12-01
• [Presentation] 神経膠腫幹細胞と神経前駆細胞における転写ネットワークの差異 (2010)
  • Author(s): 生島弘彬、宮園浩平, 他
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪国際会議場(大阪府大阪市)
  • Year and Date: 2010-09-24
• [Presentation] TGF-βシグナルのがん幹細胞と微小環境における役割 (2010)
  • Author(s): 宮園浩平
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪国際会議場(大阪府大阪市)(日本癌学会-アメリカ癌学会合同シンポジウム)(招待講演)
  • Year and Date: 2010-09-22
• [Remarks]
  • URL: http://cancer-microenvironment.jp/
• [Remarks] 文部科学省科学研究費補助金「新学術領域研究（研究領域提案型）」がん微小環境ネットワークの統合的研究
  • URL: http://cancer-microenvironment.jp/
• [Remarks] 東京大学大学院医学系研究科病因・病理学専攻分子病理学分野
  • URL: http://beta-lab.umin.ac.jp/
• [Remarks] 東京大学大学院医学系研究科病因・病理学専攻分子病理学分野
  • URL: http://beta-lab.umin.ac.jp/
• [Remarks] 文部科学省科学研究費補助金「新学術領域研究（研究領域提案型）」がん微小環境ネットワークの統合的研究
  • URL: http://cancer-microenvironment.jp/
• [Remarks] 東京大学大学院医学系研究科病因・病理学専攻分子病理学分野
  • URL: http://beta-lab.umin.ac.jp/
• [Remarks] 文部科学省科学研究費補助金「新学術領域研究（研究領域提案型）」がん微小環境ネットワークの統合的研究
  • URL: http://cancer-microenvironment.jp/