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Inhibitory mechanism of vascular endothelial cell proliferation by endostatin

Research Project

Project/Area Number 11470274
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Thoracic surgery
Research InstitutionOKAYAMA UNIVERSITY

Principal Investigator

NINOMIYA Yoshifumi  Okayama University, Graduate School of Professor Medicine and Dentistry, 大学院・医歯学総合研究科, 教授 (70126241)

Co-Investigator(Kenkyū-buntansha) YONEZAWA Tomoko  Okayama University, Graduate School of Assistant Medicine and Dentistry, 大学院・医歯学総合研究科, 助手 (30304299)
MOMOTA Ryusuke  Okayama University, Graduate School of Assistant Medicine and Dentistry, 大学院・医歯学総合研究科, 助手 (80263557)
OOHASHI Toshitaka  Okayama University, Graduate School of Lecturer Medicine and Dentistry, 大学院・医歯学総合研究科, 講師 (50194262)
植木 靖好  岡山大学, 医学部, 助手 (60304309)
Project Period (FY) 1999 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥13,900,000 (Direct Cost: ¥13,900,000)
Fiscal Year 2001: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2000: ¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 1999: ¥6,500,000 (Direct Cost: ¥6,500,000)
Keywordsendostatin / type XVIII collagen / vascular endothelial cells / type XV collagen / basement membrane
Research Abstract

Under low oxygen condition, expression of collagen XVIII gene by cultured vascular endothelial cells reduced significantly. When it was analyzed by specific monoclonal antibodies, the collagen XVIII protein level was also reduced.
Endostatin induced regression of chondrosarcoma growth and tumor angiogenesis in vivo. However, endostatin showed no effects on the proliferation and migration of chondrosarcoma cells in vitro. Next, we investigated the interactions between endostatin and endothelial cells in detail. Endostatin inhibited the migration and attachment on collagen I but did not affect proliferation of endothelial cells. Although the migration of endothelial cells was stimulated with angiogenic factors such as basic fibroblast growth factor and vascular endothelial growth factor, endostatin showed similar inhibitory effects on it in the presence or absence of stimulants.
We came to the conclusion that non-vascular BMs contain predominantly one of the two types; I.e., subepithelial basement membranes contained type XVIII in general, whereas skeletal and cardiac muscles harbored prominently type XV. But basement membranes surrounding smooth muscle cells in vascular tissues contained one or both of them, depending on their locations. Interestingly, continuous or somatic capillaries contained both type XV and type XVIII collagens in their basement membranes; however, fenestrated or specialized capillaries such as glomeruli, liver sinusoids, lung alveoli, and splenic sinusoids expressed only type XVIII chains in their basement membranes, lacking type XV chain. This observation could imply different functions of basement membranes in various tissues and organs that use different mechanisms for the endogenous control of angiogenesis.

Report

(4 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (28 results)

All Other

All Publications (28 results)

  • [Publications] Satoh M et al.: "Inhibition of poly(ADP-ribose) polymerase attemuates cerebral vasospasm after subarachnoid hemorrage in rabbits"Stroke. 32. 225-231 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Pingsheng Wu et al.: "Hypoxia down-regulates endstatin production by human micro vascular endthelial cells and pericytes"Biochem.Biophys.Res.Commun.. 288・5. 1149-1154 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Furumatsu T.et al.: "Human Chondrosarcoma secretes vascular endtherial growth factors induce tumor angiogenesis and stores bFGF for regulation of its own growth"Int.J.Cancer. 97・3. 313-322 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Furumatsu T.et al.: "Endostatin inhibits adhesive activities of endtheleal cells on type I collagen via α2βIintegrin as a possible cause of prevention"J.Biochem.(Tokyo). (発表予定). (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tomoko Y.et al.: "Epitope-defined monoclonal antibodies against multprotein collagens domain structures that type XV and XVIII collagens are expressed in specialized BM"Cell Struc Funct.. (発表予定). (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Urabe N.et al.: "Basement membrane type IV collagen molecules in choroid plexus, pia mater and capillaries in the mouse brain"Arch.Histol.Cytol.. (発表予定). (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Satoh M,Date I, Nakajima M, Takahashi K, Iseda K, Tamiya T, Ohmoto T, Ninomiya Y, Asari S.: "Inhibition of Poly(ADP-Ribose)Polymerase Attenuates Cerebral Vasospasm After Subarachnoid Hemorrhage in Rabbits."Stroke. 32. 225-231 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Pingsheng Wu, Hideto Yonekura, Hui Li, Ichiro Nozaki, Yasuko Tomono, Ichiro Naito, Yoshifumi Ninomiya and Hiroshi Yamamoto: "Hypoxia down-regulates endostatin production by human microvascularendothelial cells and pericyte."Biochem. Biophys. Res. Commun.. 288(5). 1149-54 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Furumatsu T, Nishida K, Kawai A, Namba M, Inoue H, Ninomiya Y.: "Human chondrosarcoma secretes vascular endothelial growth factor to induce tumor angiogenesis and stores basic fibroblast growth factor for regulation of its own growth."Int J Cancer.. 97(3). 313-322 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takayuki Furumatsu, Noriko Yamaguchi, Keiichiro Nishida, Akira Kawai, Toshiyuki Kunisada, Masayoshi Namba, Hajime Inoue and Yoshifumi Ninomiya: "Endostatin Inhibits Adhesive activities the of endothelial cells on type I collagen via α2β1integrin as a possible cause of prevention on chondrosarcoma growth."J. Biochem. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yasuko Tomono, Ichiro Naito, Kaori Ando, Tomoko Yonezawa, Yoshikazu Sado, Satoshi Hirakawa, Jiro Arata, Tohru Okigaki, and Yoshifumi Ninomya: "Epitope-defined monoclonal antibodies against multiplexin collagens demonstrate that type XV and XVIII collagens are expressed in specialized basement membranes."Cell Struc Funot. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Norio Urabe, Ichiro Naito, Kenji Saito, Tomoko Yonezawa, Yoshikazu Sado, Hidekatsu Yoshioka, Shozo Kusachi, Takao Tsuji, Aiji Ohtsuka, Takehito Taguchi, Takuro Murakami, and Yoshifumi Ninomiya: "Basement Membrane Type IV Collagen Molecules in Choroid Plexus, Pia Mater and Capillaries in the Mouse Brain."Arch Hitochem Cyto. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Satolu, M., et al.: "Inhibition of poly(ADP-ribose)polymerase gttinuates cerebral vasospasm after subarachnoid hemorrlage in rabbits"Stroke. 32. 225-231 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Pingsheng Wu et al.: "Hypoxia down-regulates endostatin production by human microvascular endothelial cells and pericytes"Biochem. biophys. Res. Commun.. 288・5. 1149-1154 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Furumatsu, T., et al.: "Human chondrosarcoma secretes vascular endothelial growth factor to induce tumor angiogenesis and stores basic fibroblast growth factor for regulation of its own growth"Int.J.Cancer. 97・3. 313-322 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Furumatsu, T., et al.: "Endstatin inhibits adhesive actuvities of endothelial calls on type I collagen via α2β1 integrin as appossible cause of prevention"J.Biochem(Tokyo). (発表予定). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tomono Y et al.: "epitope-defined monoclonal antibodies against multipledin collagens clemonstrales that type XV and XVIII collagens mi expressed in special yd BM"Cell Struc Funct.. (発表予定). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Wabe N et al.: "Basement menderance type TV cooagen molecules in choroid plexus, pia materand copillaries in the mouse brain"Arch.Histol Cytol.. (発表予定). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Lee G.E. et al: "Expression of the α6 chain of type IV collagen in glomerular basement membranes of healthy adult dogs."Am.J.,Vet.Res. 61. 38-41 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Petitclese E. et al: "New functions for non-collagenous domains of human collagen type IV. Novel integrin ligands inhibiting angiogenesis and tumor growth in vivo."J.Biol.Chem.. 275. 8051-8061 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Saito K. et al.: "Expression of mouse α5 (IV) and α6(IV) collagengenes in epithelial basement membranes."J.Biochem (Tokyo). 128. 427-434 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Boutaud A. et al.: "Type IV collagen of the glomerular basement membrane. Evidence that the chain specificity of network assembly is encoded by non-collagenous"J.Boiol.Chem.. 275. 30716-30724 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hisakawa S. et al.: "The brain link protein-1 (BRAL1): cDNA cloning, genomic structure, and characterization as a novel link protein expressed in adult brain."Biochem.Biophys.Res.Commun.. 276. 982-989 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] van Wezell et al.: "Ultrastructure and composition of call-exner bodies in bovine follicles"Call Tissue Res.. 296. 385-394 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nakans S et al.: "Differential Tissular Expression and Localization of Type IV collagen α^1(IV),α^2(IV),α^5(IV) and α^6(IV) chains and thair mRNAs"Laboratory Investigation. 79. 281-292 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Toth M. et al: "Biosynthesis of α^2(IV) and α^1(IV) chains of collagen IV and interactions with matrix metalloprotinases-9"J. Cell Physiol. 180. 131-139 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Lee G E et al.: "New form of X-linked dominant hereditary nephritis in dogs"Am. J. Vet. Res.. 60. 373-383 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Zheng K et al.: "Absence of the α^6(IV) chain of collagen type IV in Alport syndrome is related to a failure at the protein assembly ecol"Am. J. Pathol. 154. 1883-1891 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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