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2001 Fiscal Year Final Research Report Summary

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)
Project Period (FY) 1999 – 2001
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.

  • Research Products

    (12 results)

All Other

All Publications (12 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
  • [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
  • [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
  • [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)

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      「研究成果報告書概要(和文)」より
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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).

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      「研究成果報告書概要(欧文)」より

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Published: 2003-09-17  

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