Signaling mechanism of tumor angiogenesis.

• Project/Area Number: 17014020
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Tokyo Medical and Dental University (2007-2009); The University of Tokyo (2005-2006)
• Principal Investigator: SHIBUYA Masabumi Tokyo Medical and Dental University, 医学部, 非常勤講師 (10107427)
• Co-Investigator(Kenkyū-buntansha): 後藤 典子 東京大学, 医科学研究所, 助教授 (10251448) ; 櫻井 桂子 (櫻井 佳子) 東京大学, 医科学研究所, 助手 (10361619) ; 矢花 直幸 東京大学, 医科学研究所, 助手 (90292846)
• Project Period (FY): 2005 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥169,900,000 (Direct Cost: ¥169,900,000); Fiscal Year 2009: ¥34,000,000 (Direct Cost: ¥34,000,000); Fiscal Year 2008: ¥34,000,000 (Direct Cost: ¥34,000,000); Fiscal Year 2007: ¥34,100,000 (Direct Cost: ¥34,100,000); Fiscal Year 2006: ¥34,100,000 (Direct Cost: ¥34,100,000); Fiscal Year 2005: ¥33,700,000 (Direct Cost: ¥33,700,000)
• Keywords: VEGFR / マクロファージ / 腫瘍血管 / 血管阻害療法 / 低酸素・低栄養ストレス / VEGFR-1 / VEGFR1 / 脳腫瘍 / VEGFR2 / 単球 / トロンボスポンジン-1 / 血管新生 / VEGF / VEGF受容体 / 血管抑制因子 / シグナル伝達

Research Abstract

We demonstrated that (1) vascular endothelial growth factorreceptor-2 (VEGFR-2) utilizes unique signaling via a single tyrosine by using mutantmouse model, and (2) VEGFR-1 plays an important role in growth of tumors includingbrain tumor in vivo mostly via activation of VEGFR-1+ bone-marrow-derived cells.Furthermore, we showed that resistance of tumors against antiangiogenic therapy is partlydependent on a metabolic shift under stresses. In addition, we found new pathway for thefunction of endogenous antiangiogenic protein TSP1.

Research Products

• [Journal Article] VEGFR-1 signaling regulates the homing of bone marrow derived cells in a mouse stroke model. (2010)
  • Author(s): Beck H, Raab S, Copanaki E, Heil M, Scholz A, Shibuya M, Deller T, Machein M, Plate KH.
  • Journal Title: J. Neuropathol. Exp. Neurol. 69 Pages: 168-175
• [Journal Article] An FGF4-FRS2α-Cdx2 axis in trophoblast stem cells induces BMP4 to regulate proper growth of early mouse embryos. (2010)
  • Author(s): Murohashi M, Nakamura T, Tanaka S, Ichise T, Yoshida N, Yamamoto T, Shibuya M, Schlessinger J, Gotoh N.
  • Journal Title: Stem Cells. 28 Pages: 113-121
• [Journal Article] Hypoxia and Low Nutrition Double Stress Induces Aggressiveness in a Murine Model of Melanoma. (2009)
  • Author(s): Osawa, T., Muramatsu, M., Watanabe, M., Shibuya, M.
  • Journal Title: Cancer Sci. 100 Pages: 844-851
  • NAID: 10025145482
• [Journal Article] M-CSF inhibition selectively targets pathological angiogenesis and lymphangiogenesis. (2009)
  • Author(s): Kubota Y, Takubo K, Shimizu T, Ohno H, Kishi K, Shibuya M, Saya H, Suda T.
  • Journal Title: J Exp Med. 206 Pages: 1089-102
• [Journal Article] VEGFR-1 regulates adult olfactory bulb neurogenesis and migration of neural progenitors in the rostral migratory stream in vivo. (2009)
  • Author(s): Wittko IM, Schanzer A, Kuzmichev A, Schneider FT, Shibuya M, Raab S, Plate KH
  • Journal Title: J. Neurosci. 29 Pages: 8704-8714
• [Journal Article] VEGF Receptor-2 Y1175 signaling controls VEGF-induced vWF release from endothelial cells via PLCgamma1- and PKA-dependent pathways. (2009)
  • Author(s): Xiong Y, Huo Y, Chen C, Zeng H, Lu X, Wei C, Ruan C, Zhang X, Hu Z, Shibuya M, Luo J
  • Journal Title: J Biol Chem 284 Pages: 23217-2324
• [Journal Article] Mechanism of Inhibition of Tumor Angiogenesis by beta-Hydroxyisovalerylshikonin (2009)
  • Author(s): Komi Y, et al.
  • Journal Title: Cancer Sci. 100 Pages: 269-277
  • Peer Reviewed
• [Journal Article] Hypoxia and Low Nutrition Double Stress Induces Aggressiveness in a Murine Model of Melanoma (2009)
  • Author(s): Osawa T, et al.
  • Journal Title: Cancer Sci. 100 Pages: 844-851
  • Peer Reviewed
• [Journal Article] Soluble Flt-1 gene transfer ameliorates neointima formation after wire injury in flt-1 tyrosine kinase-deficient mice (2009)
  • Author(s): Koga J, et al.
  • Journal Title: Arterioscler Thromb Vasc Biol. 29 Pages: 458-464
  • Peer Reviewed
• [Journal Article] M-CSF inhibition selectively targets pathological angiogenesis and lymphangiogenesis (2009)
  • Author(s): Kubota Y, et al.
  • Journal Title: J Exp Med. 206 Pages: 1089-1102
  • Peer Reviewed
• [Journal Article] VEGFR-1 regulates adult olfactory bulb neurogenesis and migration of neural progenitors in the rostral migratory stream in vivo (2009)
  • Author(s): Wittko IM, et al.
  • Journal Title: J Neurosci. 29 Pages: 8704-8714
  • Peer Reviewed
• [Journal Article] Growth inhibition of AML cells with specific chromosome abnormalities by monoclonal antibodies to receptors for vascular endothelial growth factor (2009)
  • Author(s): Imai N, et al.
  • Journal Title: Leukemia Res. 33 Pages: 1650-1657
  • Peer Reviewed
• [Journal Article] VEGF Receptor-2 Y1175 signaling controls VEGF-induced vWF release from endothelial cells via PLCgammal- and PKA-dependent pathways (2009)
  • Author(s): Xiong Y, et al.
  • Journal Title: J Biol Chem. 284 Pages: 23217-2324
  • Peer Reviewed
• [Journal Article] Effect of recombinant placental growth factor 2 on hypertension induced by full-length mouse soluble fms-like tyrosine kinase 1 adenoviral vector in pregnant mice (2009)
  • Author(s): Suzuki H, et al.
  • Journal Title: Hypertension 54 Pages: 1129-1135
  • Peer Reviewed
• [Journal Article] Professor Hidesaburo Hanafusa : A 50-Year Quest for the Molecular Basis of Cancer (2009)
  • Author(s): Shibuya, M.
  • Journal Title: J Biochem. 146 Pages: 3-5
  • NAID: 10025187222
• [Journal Article] Brain angiogenesis in developmental and pathological processes : therapeutic aspects of vascular endothelial growth factor (2009)
  • Author(s): Shibuya, M.
  • Journal Title: FEBS J. 276 Pages: 4636-4643
  • Peer Reviewed
• [Journal Article] Unique signal transduction of VEGF-A and VEGF-E (2009)
  • Author(s): Shibuya, M.
  • Journal Title: Biochem Soc Trans. 37(Pt 6) Pages: 1161-1166
  • Peer Reviewed
• [Journal Article] Mechanism of Inhibition of Tumor Angiogefiesis by beta-Hydroxyisovaler ylshikonin (2009)
  • Author(s): Komi Y, et.al.
  • Journal Title: Cancer Sci 100 Pages: 269-277
  • Peer Reviewed
• [Journal Article] Hypoxia and Low Nutrition Double Stress Induces Aggressiveness in a Murine Model of Melanoma (2009)
  • Author(s): Osawa, T., et.al.
  • Journal Title: Cancer Sci 100 Pages: 844-851
  • Peer Reviewed
• [Journal Article] Growth inhibition of AML cells with specific chromosome abnormalities by monoclonal antibodies to receptors for vascular endothelial growth factor (2009)
  • Author(s): Imai N, et.al.
  • Journal Title: Leuk Res (in press)
  • Peer Reviewed
• [Journal Article] Brain angiogenesis : Therapeutic aspects of VEGF (2009)
  • Author(s): Shibuya, M
  • Journal Title: FEBS J (in press)
  • Peer Reviewed
• [Journal Article] VEGFR1 Tyrosine Kinase Signaling Promotes Lymphangiogenesis as Well as Angiogenesis Indirectly via Macrophage Recruitment. (2008)
  • Author(s): Murakami, M. Zheng Y, Hirashima M, Suda T, Morita Y, Ooehara J, Ema H, Fong GH, Shibuya M
  • Journal Title: Arterioscler Thromb Vasc Biol 28 Pages: 658-664
• [Journal Article] The S100A8-serum amyloid A3-TLR4 paracrine cascade establishes a pre-metastatic phase. (2008)
  • Author(s): Hiratsuka S, Watanabe A, Sakurai Y, Akashi-Takamura S, Ishibashi S, Miyake K, Shibuya M, Akira S, Aburatani H, Maru Y
  • Journal Title: Nature Cell Biol. 10 Pages: 1349-1355
• [Journal Article] Differential function of Tie2 at cell-cell contacts and cell-substratum contacts regulated by angiopoietin-1. (2008)
  • Author(s): Fukuhara S, Sako K, Minami T, Noda K, Kim HZ, Kodama T, Shibuya M, Takakura N, Koh GY, Mochizuki N.
  • Journal Title: Nature Cell Biol 10 Pages: 513-526
• [Journal Article] Flt-1 signaling in macrophages promotes glioma growth in vivo. (2008)
  • Author(s): Kerber M, Reiss Y, Wickersheim A, Jugold M, Kiessling F, Heil M, Tchaikovski V, Waltenberger J, Shibuya M, Plate KH, Machein MR
  • Journal Title: Cancer Res 68 Pages: 7342-7351
• [Journal Article] Blocking VEGFR-3 suppresses angiogenic sprouting and vascular network formation. (2008)
  • Author(s): Tammela T, Zarkada G, Wallgard E, Murtomaki A, Suchting S, Wirzenius M, Waltari M, Hellstrom M, Schomber T, Peltonen R, Freitas C, Duarte A, Isoniemi H, Laakkonen P, Christofori G, Yla-Herttuala S, Shibuya M, Pytowski B, Eichmann A, Betsholtz C, Alitalo K
  • Journal Title: Nature 54 Pages: 656-660
• [Journal Article] Anti-tumor activity and tumor vessel normalization by the vascular endothelial growth factor receptor tyrosine kinase inhibitor KRN951 in a rat peritoneal disseminated tumor model (2008)
  • Author(s): Taguchi E, et.al.
  • Journal Title: Cancer Sci 99 Pages: 623-630
  • Peer Reviewed
• [Journal Article] VEGFR1 Tyrosine Kinase Signaling Promotes Lymphangiogenesis as Well as Angiogenesis Indirectly via Macrophage Recruitment (2008)
  • Author(s): Murakami M, et.al.
  • Journal Title: Arterioscler Thromb Vasc Biol 28 Pages: 658-664
  • Peer Reviewed
• [Journal Article] Cisplatin treatment increases survival and expansion of a highly tumorigenic side-population fraction by upregulating VEGF/Flt1 autocrine signaling (2008)
  • Author(s): Tsuchida R, et.al.
  • Journal Title: Oncogene 27 Pages: 3923-3934
  • Peer Reviewed
• [Journal Article] Regulation of clathrin-mediated endocytosis by p53 (2008)
  • Author(s): Endo Y, et.al.
  • Journal Title: Genes Cels. 13 Pages: 375-386
  • Peer Reviewed
• [Journal Article] Differential function of Tie2 at cell-cell contacts and cell-substratum contacts regulated by angiopoietin-1 (2008)
  • Author(s): Fukuhara S, et.al.
  • Journal Title: Nat Cell Biol 10 Pages: 513-526
  • Peer Reviewed
• [Journal Article] Blocking VEGFR-3 suppresses angiogenic sprouting and vascular network formation (2008)
  • Author(s): Tammela T, et.al.
  • Journal Title: Nature 54 Pages: 656-660
  • Peer Reviewed
• [Journal Article] Flt-1 signaling in macrophages promotes glioma growth in vivo (2008)
  • Author(s): Kerber M, et.al.
  • Journal Title: Cancer Res 68 Pages: 7342-7351
  • Peer Reviewed
• [Journal Article] Inhibition of choroidal neovascularization by blocking vascular endothelial growth factor receptor tyrosine kinase (2008)
  • Author(s): Kami J, et.al.
  • Journal Title: Jpn J Ophthalmol 52 Pages: 91-98
  • Peer Reviewed
• [Journal Article] Vascular Endothelial Growth Factor Receptor-1 Regulates Postnatal Anaioaenesis Through Inhibition of the Excessive Activation of Akt (2008)
  • Author(s): Nishi JI, et.al.
  • Journal Title: Circulation Res 103 Pages: 261-268
  • Peer Reviewed
• [Journal Article] Novel Role for VEGF-Receptor-1 and its Ligand VEGF-B in Motor Neuron Degeneration (2008)
  • Author(s): Poesen K, et.al.
  • Journal Title: J. Neurosci 28 Pages: 10451-10459
  • Peer Reviewed
• [Journal Article] The S100A8-serum amyloid A3-TLR4 paracrine cascade establishes a Pre-metastatic phase (2008)
  • Author(s): Hiratsuka S, et.al.
  • Journal Title: Nat Cell Biol 10 Pages: 1349-1355
  • Peer Reviewed
• [Journal Article] Involvement of vascular endothelial growth factor receptor-1 in rheumat oid arthritis (2008)
  • Author(s): Murakami M, et.al.
  • Journal Title: Inflammation and Regeneration 28 Pages: 78-85
• [Journal Article] VEGF receptor signal transduction (2008)
  • Author(s): Li X., et.al.
  • Journal Title: Methods Enzymol 443 Pages: 261-284
• [Journal Article] Anti-tumor activity and tumor vessel normalization by the vascular endothelial growth factor receptor tyrosine kinase inhibitor KRN951 in a rat peritoneal disseminated tumor model. (2008)
  • Author(s): Taguchi E, et. al.
  • Journal Title: Cancer Sci. (In press)
  • Peer Reviewed
• [Journal Article] VEGFR1 Tyrosine Kinase Signaling Promotes Lymphangiogenesis as Well as Angiogenesis Indirectly via Macrophage Recruitment. (2008)
  • Author(s): Murakami M, et. al.
  • Journal Title: Arterioscler Thromb Vasc Biol. (In press)
  • Peer Reviewed
• [Journal Article] Cisplatin treatment increases survival and expansion of a highly tumorigenic side-population fraction by upregulating VEGF/Flt1 autocrine signaling. (2008)
  • Author(s): Tsuchida R, et. al.
  • Journal Title: Oncogene (In press)
  • Peer Reviewed
• [Journal Article] Chimeric VEGF-ENZ7/PlGF Specifically Binding to VEGFR-2 Accelerates Skin Wound Healing via Enhancement of Neovascularization. (2007)
  • Author(s): Zheng Y, Watanabe M, Kuraishi T, Hattori S, Kai C, Shibuya M
  • Journal Title: Arterioscler, Thromb, Vasc. Biol. 27 Pages: 503-511
• [Journal Article] Distinct vascular endothelial growth factor signals for lymphatic vessel enlargement and sprouting. (2007)
  • Author(s): Wirzenius, M., Tammela, T., Uutelaff, M., He, Y., Odorisio, T., Sambruno, G., Nagy, JA, Dvorak, HF, Yla-Herttuala, S., Shibuya, M., Alitalo, K
  • Journal Title: J. Exp. Med. 204 Pages: 1431-1340
• [Journal Article] A novel anti-angiogenic pathway of thrombospondin-1 mediated by suppression of the cell cycle. (2007)
  • Author(s): Yamauchi, M., Imajoh-Ohmi, S., Shibuya, M
  • Journal Title: Cancer Science 98 Pages: 1491-1497
  • NAID: 10019999111
• [Journal Article] Therapeutic Angiogenesis Using Novel Vascular Endothelial Growth Factor-E/Human Placental Growth Factor Chimera Genes. (2007)
  • Author(s): Inoue N, et. al.
  • Journal Title: Arterioscler Thromb Vasc Biol. 27 Pages: 99-105
  • Peer Reviewed
• [Journal Article] {alpha} 4-integrin+ endothelium derived from primate embryonic stemcells generates both primitive and definitive hematopoietic cells. (2007)
  • Author(s): Shinoda G, et. al.
  • Journal Title: Blood 109 Pages: 2406-2415
  • Peer Reviewed
• [Journal Article] Chimeric VEGF-E_<NZ7>/PlGF Specifically Binding to VEGFR-2 Accelerates Skin Wound Healing via Enhancement of Neovascularization. (2007)
  • Author(s): Zheng Y, et. al.
  • Journal Title: Arterioscler, Thromb, Vasc. Biol. 27 Pages: 503-511
  • Peer Reviewed
• [Journal Article] Distinct vascular endothelial growth factor signals for lymphatic vessel enlargement and sprouting. (2007)
  • Author(s): Wirzenius, M, et. al.
  • Journal Title: J. Exp. Med. 204 Pages: 1431-1340
  • Peer Reviewed
• [Journal Article] Identification of functional endothelial progenitor cells suitable for the treatment of ischemic tissue using human umbilical cord blood. (2007)
  • Author(s): Nagano M, et. al.
  • Journal Title: Blood 110 Pages: 151-160
  • Peer Reviewed
• [Journal Article] A novel anti-angiogenic pathway of thrombospondin-1 mediated by suppression of the cell cycle. (2007)
  • Author(s): Yamauchi M., et. al.
  • Journal Title: Cancer Science 98 Pages: 1491-1497
  • Peer Reviewed
• [Journal Article] The lysine 831 of vascular endothelial growth factor receptor 1 is a novel target of methylation by SMYD3. (2007)
  • Author(s): Kunizaki M, et. al.
  • Journal Title: Cancer Res. 67 Pages: 10759-1065
  • Peer Reviewed
• [Journal Article] Ligand-independent activation of vascular endothelial growth factor receptor 1 by low-density lipoprotein. (2007)
  • Author(s): Usui R, et. al.
  • Journal Title: EMBO Rep. 8 Pages: 1155-1161
  • Peer Reviewed
• [Journal Article] Inhibitory Smad transcription factors protect arterial endothelial endothelial cells from apoptosis induced by BMP4. (2006)
  • Author(s): Kiyono, M., Shibuya, M
  • Journal Title: Oncogene 25 Pages: 7131-7137
• [Journal Article] Chimeric VEGF-ENZ7/PlGF Promotes Angiogenesis via VEGFR-2 without Significant Enhancement of Vascular Permeability and Inflammation. (2006)
  • Author(s): Zheng, Y., Murakami, M., Takahashi, H., Yamauchi, M., Kiba, A., Yamaguchi, S., Yabana, N., Alitalo, K., Shibuya, M
  • Journal Title: Arterioscler, Thromb, Vasc. Biol. 26 Pages: 2019-2026
• [Journal Article] Signaling of vascular endothelial growth factor receptor-1 tyrosine kinase promotes rheumatoid arthritis through activation of monocyte/macrophages. (2006)
  • Author(s): Murakami, M., Iwai, S., Hiratsuka, S., Yamauchi, M., Nakamura, K., Iwakura, Y., Shibuya, M
  • Journal Title: Blood 108 Pages: 1849-1856
• [Journal Article] Corneal avascularity is due to soluble VEGF receptor-1. (2006)
  • Author(s): Ambati BK, Nozaki M, Singh N, Takeda A, JaniPD, Suthar T, Albuquerque RJ, Richter E, Sakurai E,Newcomb MT, Kleinman ME, Caldwell RB, Lin Q,Ogura Y, Orecchia A, Samuelson DA, Agnew DW,St Leger J, Green WR, Mahasreshti PJ, Curiel DT,Kwan D, Marsh H, Ikeda S, Leiper LJ, CollinsonJM, Bogdanovich S, Khurana TS, Shibuya M,Baldwin ME, Ferrara N, Gerber HP, De Falco S,Witta J, Baffi JZ, Raisler BJ, Ambati J.
  • Journal Title: Nature 443 Pages: 993-997
• [Journal Article] Cell adhesion and prostate tumor-suppressor activity of TSLL2/IGSF4C, an immunoglobulin superfamily molecule homologous to TSLC1/IGSF4 (2006)
  • Author(s): Williams YN, et al.
  • Journal Title: Oncogene 25 Pages: 1446-1453
• [Journal Article] Claesson-Welsh L. Signal transduction by VEGF receptors in regulation of angiogenesis and lymphangiogenesis (2006)
  • Author(s): Shibuya M.
  • Journal Title: Exp Cell Res. 312 Pages: 549-560
• [Journal Article] Bastadin 6, a spongean brominated tyrosine derivative, inhibits tumor angiogenesis by inducing selective apoptosis to endothelial cells (2006)
  • Author(s): Aoki S.et al.
  • Journal Title: Anticancer Drugs 17 Pages: 269-278
• [Journal Article] Inhibitory Smad transcription factors protect arterial endothelial endothelial cells from apoptosis induced by BMP4 (2006)
  • Author(s): Kiyono M. et al.
  • Journal Title: Oncogene 25 Pages: 7131-7137
• [Journal Article] Inhibition of tumor growth with antiangiogenic cancer vaccine using epitope peptides derived from human vascular endothelial growth factor receptor 1 (2006)
  • Author(s): Ishizaki H. et al.
  • Journal Title: Clin Cancer Res. 12 Pages: 5841-5849
• [Journal Article] Synthesis and biological evaluation of benzamides and benzamidines as selective inhibitors of VEGFR tyrosine kinases (2006)
  • Author(s): Nakamura H. et al.
  • Journal Title: Bioorg Med Chem Lett. 16 Pages: 37-51
• [Journal Article] Membrane-fixation of VEGFR1 ligand-binding domain is important for vasculogenesis/angiogenesis in mice. (2005)
  • Author(s): Hiratsuka, S., Nakao, K., Nakamura, K., Katsuki, M., Maru, Y., Shibuya, M
  • Journal Title: Mol. Cell. Biol. 25 Pages: 346-354
• [Journal Article] VEGF-A is involved in guidance of VEGF-receptor-positive cells to the anterior portion of early embryos. (2005)
  • Author(s): Hiratsuka, S., Kataoka, Y., Nakao, K., Nakamura, K., Morikawa, S., Tanaka, S., Katsuki, M., Maru, Y., Shibuya, M
  • Journal Title: Mol. Cell. Biol. 25 Pages: 355-363
• [Journal Article] Essential role of Flk-1 (vascular endothelial growth factor receptor-2) tyrosine residue-1173 in vasculogenesis in mice. (2005)
  • Author(s): Sakurai, Y., Ohgimoto, K., Kataoka, Y., Yoshida, N., Shibuya M
  • Journal Title: Proc. Natl. Acad. Sci. USA 102 Pages: 1076-1081
• [Journal Article] Vascular endothelial growth factor receptor-1 signaling is essential for osteoclast development and bone-marrow formation in CSF-1-deficient mice. (2005)
  • Author(s): Niida, S., Kondo, T., Hiratsuka, S., Hayashi, S. -I., Amizuka, N., Noda, T., Ikeda, K., Shibuya, M
  • Journal Title: Proc. Natl. Acad. Sci. USA 102 Pages: 14016-14021
• [Journal Article] VEGF-A is involved in guidance of VEGF-receptor-positive cells to the anterior portion of early embryos. (2005)
  • Author(s): Hiratsuka, S., Kataoka, Y., Nakao, K., Nakamura, K., Morikawa, S., Tanaka, S., Katsuki, M., Maru, Y., Shibuya, M.
  • Journal Title: Mol.Cell.Biol. 25 Pages: 355-363
• [Journal Article] The docking protein FRS2a is an essential component of multiple FGF responses during early mouse development. (2005)
  • Author(s): Gotoh, N., Manova, K., Tanaka, S., Murohashi, M., Hadari, Y., Lee, A., Hamada, Y., Hiroe, T., Ito, M., Kurihara, T., Nakazato, H., Shibuya, M., Lax, I., Lacy, E., Schlessinger, J.
  • Journal Title: Mol.Cell.Biol. 25 Pages: 4105-4116
• [Journal Article] Rationale for antiangiogenic cancer therapy with vaccination using epitope peptides derived from human vascular endothelial growth factor receptor 2. (2005)
  • Author(s): Wada, S., Tsunoda, T., Baba, T., Primus, J., Kuwano, H., Shibuya, M., Tahara, H.
  • Journal Title: Cancer Res. 65 Pages: 4939-4946
• [Journal Article] Essential role of Shp2-binding sites on FRS2{alpha} for corticogenesis and for FGF2-dependent proliferation of neural progenitor cells. (2005)
  • Author(s): Yamamoto, S., Yoshino, I., Shimazaki, T., Murohashi, M., Hevner, RF., Lax, I., Okano, H., Shibuya, M., Schlessinger, J., Gotoh, N.
  • Journal Title: Proc.Natl.Acad.Sci.U.S.A. 102 Pages: 15983-15988
• [Journal Article] Vascular endothelial growth factor receptor-1 signaling is essential for osteoclast development bone-marrow formation in CSF-1-deficient mice. (2005)
  • Author(s): Niida, S., Kondo, T., Hiratsuka, S., Hayashi, S.-I., Amizuka, N., Noda, T., Ikeda, K., Shibuya, M.
  • Journal Title: Proc.Natl.Acad.Sci.U.S.A. 102 Pages: 14016-14021
• [Journal Article] Locating inositol 1,4,5-trisphosphate in the nucleus and neuronal dendrites with genetically encoded fluorescent indicators. (2005)
  • Author(s): Sato, M., Ueda, Y., Shibuya, M., Umezawa, Y.
  • Journal Title: Anal Chem. 77 Pages: 4751-4758
• [Presentation] 血管内皮細胞の増殖シグナルとがん分子標的 (2009)
  • Author(s): 渋谷正史
  • Organizer: 岩手医科大学・化学療法基盤情報支援班共催シンポジウム「抗がん剤創薬の新たな展開」
  • Place of Presentation: 盛岡
  • Year and Date: 2009-01-16
• [Presentation] A Unique Signal Transduction of VEGF Family Members, VEGF-A and VEGF-E. (2009)
  • Author(s): Shibuya, M
  • Organizer: in the Int. Symposium on the Molecular and cellular mechanisms of angiogenesis
  • Place of Presentation: Chester Univ., UK(invited speaker, plenary lecture)
• [Presentation] VEGF-dependent and -independent regulation of angiogenesis (2009)
  • Author(s): Shibuya, M
  • Organizer: in 7th Int. Symposium on the Biology of Endothelial Cells
  • Place of Presentation: Vienna, Austria(invited speaker)
• [Presentation] Involvement of VEGF-VEGFR System in the Progression of Cancer including Brain Tumors (2009)
  • Author(s): Shibuya, M
  • Organizer: 3rd Quandrennial Meeting of the World Federation of Neuro-Oncology
  • Place of Presentation: Yokohama, Japan(invited speaker)
• [Presentation] VEGF-dependent and -independent regulation of angiogenesis (2009)
  • Author(s): Shibuya, M
  • Organizer: KSMBMB
  • Place of Presentation: Seoul, Korea(invited speaker)
• [Presentation] Involvement of VEGF-VEGFR System in the Progression of Cancer including Brain Tumors (2009)
  • Author(s): 渋谷正史
  • Organizer: 3^<rd> Quandrennial Meeting of the World Federation of Neuro-Oncology
  • Place of Presentation: Yokohama, Japan
• [Presentation] A Unique Signal Transduction of VEGF Family Members, VEGF-A and VEGF-E (2009)
  • Author(s): 渋谷正史(plenary lecture)
  • Organizer: the Int.Symposium on the Molecular and cellular mechanisms of angiogenesis
  • Place of Presentation: Chester Univ., UK
• [Presentation] VEGF-dependent and -independent regulation of angiogenesis (2009)
  • Author(s): 渋谷正史
  • Organizer: 7^<th> Int.Symposium on the Biology of Endothelial Cells
  • Place of Presentation: Vienna, Austria
• [Presentation] VEGF-dependent and -independent regulation of angiogenesis (2009)
  • Author(s): 渋谷正史
  • Organizer: KSMBMB
  • Place of Presentation: Seoul, Korea
• [Presentation] 血管内皮増殖因子VEGFによる血管新生の分子機構 (2008)
  • Author(s): 渋谷正史
  • Organizer: 第2回数理医学研究会
  • Place of Presentation: 大阪
  • Year and Date: 2008-11-29
• [Presentation] 低酸素・低栄養ストレスに対する癌細胞の抵抗性の問題 (2008)
  • Author(s): 大澤毅、他
  • Organizer: 日本癌学会学術総会(シンポジウム)
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-28
• [Presentation] VEGF-dependent and-independent regulation of angiogenesis (2008)
  • Author(s): Shibuya, M.
  • Organizer: US-Japan Cancer Research Workshop
  • Place of Presentation: Kyoto
  • Year and Date: 2008-03-19
• [Presentation] VEGF-dependent and independent regulation of angiogenesis. (2008)
  • Author(s): Shibuya, M
  • Organizer: International Symposium, Vascular Differentiation and Remodeling
  • Place of Presentation: Frankfurt, Germany(invited speaker)
• [Presentation] VEGFR-1 is involved in tumor-growth and metastasis including melanoma. (2008)
  • Author(s): Shibuya, M
  • Organizer: The IPCC (International Pigment Cell Conference)-Melanoma Meeting-
  • Place of Presentation: Sapporo(invited speaker)
• [Presentation] VEGF-dependent and -independent regulation of angiogenesis. (2008)
  • Author(s): Shibuya, M
  • Organizer: The US-Japan Cancer Research Workshop
  • Place of Presentation: Kyoto(invited speaker)
• [Presentation] VEGFR-1 is involved in tumor-growth and metastasis including melanoma (2008)
  • Author(s): Shibuya, M
  • Organizer: The IPCC (International Pigment Cell Conference)-Melanoma Meeting
  • Place of Presentation: Sapporo
• [Presentation] VEGF-dependent and independent regulation of angiogenesis (2008)
  • Author(s): Shibuya M
  • Organizer: International Symposium, Vascular Differentiation and Remodeling
  • Place of Presentation: Frankfurt, Germany
• [Presentation] Hypoxia and low nutrition double-deprivation stress induces tumor aggressiveness (2008)
  • Author(s): Osawa T., et.al.
  • Organizer: 3rd European Conference on Tumor Angiogenesis and Antiangiogenic Therapy
  • Place of Presentation: Padova, Italy
• [Presentation] VEGFとその受容体による血管新生の制御 (2008)
  • Author(s): 渋谷正史
  • Organizer: 日本血液学会
  • Place of Presentation: 京都
• [Presentation] A unique signal transduction of VEGF receptors involved in tumor angiogenesis and metastasis. (2007)
  • Author(s): Shibuya, M
  • Organizer: The 22nd Nagoya International Cancer Treatment Symposium
  • Place of Presentation: Nagoya(invited speaker)
  • Year and Date: 2007-10-25
• [Presentation] VEGFR1 is involved in a variety of diseases, tumor growth/metastasis and rheumatoid arthritis. (2007)
  • Author(s): Shibuya, M
  • Organizer: ESH EuroConference on Angiogenesis
  • Place of Presentation: Albufeira, Portugal(invited speaker)
• [Presentation] VEGF-dependent and -independent regulation of angiogenesis (2007)
  • Author(s): Shibuya, M
  • Organizer: The Joint Scientific Meeting of Vascular Biology Organization in Asia Pacific Region
  • Place of Presentation: Tainan, Taiwan(invited speaker)
• [Presentation] A unique signal transduction of VEGF receptors is involved in tumor angiogenesis and metastasis (2007)
  • Author(s): Shibuya, M
  • Organizer: Third International Conference on Tumor-stroma interaction
  • Place of Presentation: Ascona, Switzerland(invited speaker)
• [Presentation] VEGF-dependent and independent regulation of angiogenesis (2007)
  • Author(s): Shibuya, M
  • Organizer: The First Pacific Meeting for Angiogenesis and Lymphangiogenesis
  • Place of Presentation: Jeju Island, Korea(invited speaker)
• [Presentation] VEGF-receptor signaling, and its application for pro-angiogenic therapy (2006)
  • Author(s): Shibuya, M
  • Organizer: ESH (European School of Hematology) Vascular Biology Meeting
  • Place of Presentation: Cannes, France(invited speaker)
• [Presentation] VEGF-dependent and independent regulation of angiogenesis. (2006)
  • Author(s): Shibuya, M
  • Organizer: 20th IUBMB-Kyoto, Symposium on angiogenesis and lymphangiogenesis.
  • Place of Presentation: Kyoto, Japan(invited speaker, chairman)
• [Presentation] VEGF signaling toward angiogenesis and vascular permeability. (2006)
  • Author(s): Shibuya, M
  • Organizer: KCIST 2006-Vascular Biology and Human Disease
  • Place of Presentation: Anmyondo, Korea(invited speaker)
• [Presentation] Involvement of VEGFR-1 in lymphangiogenesis in vivo (2006)
  • Author(s): Shibuya, M
  • Organizer: Gordon Research Conference on lymphangiogenesis
  • Place of Presentation: Les Diablerets, Switzerland(invited speaker)
• [Presentation] Involvement of VEGF and its receptor system in tumor growth and metastasis. (2006)
  • Author(s): Shibuya, M
  • Organizer: The Joint Meeting of 3rd ISC-ICCT and 11th ISCC
  • Place of Presentation: Tokyo(invited speaker)
• [Presentation] Molecular Mechanism of Angiogenesis (2005)
  • Author(s): Shibuya, M
  • Organizer: Third European Symposium on Vascular Biology and Medicine
  • Place of Presentation: Hamburg, Germany(invited speaker, Keynote lecture)
  • Year and Date: 2005-09-30
• [Presentation] VEGF-dependent and independent regulation of angiogenesis (2005)
  • Author(s): Shibuya, M
  • Organizer: ESH (European School of Hematology) Vascular Biology Meeting.
  • Place of Presentation: Spain(invited speaker)
• [Presentation] Molecular basis of angiogenesis (2005)
  • Author(s): Shibuya, M
  • Organizer: Korea-Japan Vascular Biology Meeting
  • Place of Presentation: Korea(invited speaker)
• [Presentation] VEGF-receptor signaling towards angiogenesis and vascular permeability (2005)
  • Author(s): Shibuya, M
  • Organizer: Gordon Research Conference, Angiogenesis and Microcirculation
  • Place of Presentation: Rhod-island, USA(invited speaker)
• [Presentation] Novel VEGF family members define the differential signals for angiogenesis and vascular permeability (2005)
  • Author(s): Shibuya, M
  • Organizer: ESH Angiogenesis Meeting
  • Place of Presentation: Ascona, Switzerland(invited speaker)
• [Book] BMB Rep (2008)
  • Author(s): Shibuya M
  • Total Pages: 9
  • Publisher: Vascular endothelial growth factor-dependent and-independent regulation of angiogenesis
• [Patent(Industrial Property Rights)] 骨形成因子をもちいた癌増殖抑制法 (2009)
  • Inventor(s): 渋谷正史、土田里香、大澤毅
  • Industrial Property Rights Holder: 東京医科歯科大学
  • Industrial Property Number: 2009-176442
  • Filing Date: 2009-07-29
• [Patent(Industrial Property Rights)] 培養血管内皮細胞株、及びそれを用いたスクリーニング方法 (2006)
  • Inventor(s): 渋谷 正史, 山口 幸子, 山内 麻衣
  • Industrial Property Rights Holder: 渋谷 正史
  • Industrial Property Number: 2006-071429
  • Filing Date: 2006-03-15