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Analysis of regulation of host defense response by osteopopontin and its applocation to diagnosis and therapy strategy

Research Project

Project/Area Number 10557024
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section展開研究
Research Field Experimental pathology
Research InstitutionHOKKAIDO UNIVERSITY

Principal Investigator

UEDE Toshimitsu  Hokkaido Univ., Inst.Genet.Med., Prof., 遺伝子病制御研究所, 教授 (00160185)

Co-Investigator(Kenkyū-buntansha) MAEDA Masahiro  Meneki Seibutsu Co.Ltd., Chief., 次長
村上 正晃  北海道大学, 免疫科学研究所, 助手 (00250514)
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥11,100,000 (Direct Cost: ¥11,100,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1999: ¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 1998: ¥5,200,000 (Direct Cost: ¥5,200,000)
Keywordsosteopontin / cancer / prognosis / atherosclerosis / 肉芽腫 / アレル / トランスジェニックマウス / iNOS / ELISA / CD44v / β1インテグリン / 細胞接着 / 細胞遊走 / 転移
Research Abstract

1. Highly metastatic adenocarcinoma cells tend to secrete osteopontin(OPN). OPN binds to β1 integrin-containing receptors in an autocrine fashion and induce motility of tumor cells. The association of β1 integrins with CD44v on tumor cell surface is essential for OPN-induced tumor cell motility.
2. The new-vessel formation as defined by CD34 positive endothels was significantly increased in OPN and VEGF positive stage I lung adenocarcinoma tissues and corelated very well with poor prognosis of patients.
3. Upon high fat diet feeding, OPN transgenic mice developed considerably severe atherosclerosis as compared to control mice. In OPN transgenic mice, macrophages within atherosclerotic lesions expressed significant levels of OPN.
4. Upon intravenous injection of zymosan, mice develoved liver granuloma, the development of granuloma was significantly inhibited by simultaneous injection of anti-OPN antibody, indicating the critical role of OPN in the granuloma development.

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (44 results)

All Other

All Publications (44 results)

  • [Publications] Y.Wang: "Increased expression of osteopontin in activated kupffer cells and hepatic macrophages during macrophage migration in Propionibacterium acnes-treated rat liver."J.Gastroenterol.. 69(5). 696-701 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] T.Takahashi: "Immunologic self-tolerance maintained by CD25 (+) CD4 (+) regulatory T cells constitutively expressing cytotoxic T lymphocyte-associated antigen 4."J.Exp.Med.. 192(2). 303-310 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] N.Shijubo: "Vascular endothelial growth factor and osteopontin in tumor biology."Crit.Rev.Oncog.. 11(2). 135-146 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] S.Kon: "Antibodies to different peptides in osteopontin reveal complexities in the various secreted forms."J.Cell.Biochem.. 77(3). 487-498 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] S.Chiba: "The role of osteopontin in the development of granulomatous lesions in lung."Microbiol.Immunol.. 44(4). 319-332 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Takemoto: "Enhanced expression of osteopontin in human diabetic and analysis of its functional role in accelerated atherogenesis."Arteriouscler.Thromb.Vasc.Biol.. 20(3). 624-628 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] R.Kawashima: "Expression of osteopontin in kupffer cells and hepatic macrophages and Stellate cells inn rat liver after carbon tetrachloride intoxication : a possible factor for macrophage migration into hepatic necrotic areas."Biochem.Biophys.Res.Commun.. 256(3). 527-531 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] N.Shijubo: "Vascular endothelial growth factor and osteopontin in stage I lung adenocarcinoma."Am.J.Respir.Crit.Care.Med.. 160(4). 1269-1273 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] T.Yasui: "Quantification of osteopontin in the urine of healthy and stone-forming men."Urol.Res.. 27(4). 225-230 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] YU.Katagiri: "CD44 variants but not CD44s cooperate with β1-containing integrins to permit cells to bind to osteopontin independently of arginine-glycine-aspartic acid, thereby stimulating cell motility and chemotaxis."Cancer Res.. 59(1). 219-226 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] H.Hotta: "Detection of various epitopes of murine osteopontin by monoclonal antibodies."Biochem.Biophys.Res.Commun.. 257(1). 6-11 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] J.Iizuka: "Introduction of an osteopontin gene confers the increase in B1 cell population and the production of anti-DNA autoantibodies."Arteriouscler.Thromb.Vasc.Biol.. 20(3). 624-628 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] K.Shigehara: "Immunolocarization of extracellular matrix proteins and integrins in sarcoid lymph nodes."Virchows Arch.. 443(1). 55-61 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] T.Fukumoto: "Peptide mimics of the CTLA4-binding domain stimulate T-cell proliferation."Nat.Biotechnol.. 16(3). 267-270 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Y.Wang, S.Mochida, R.Kawashima, M.Inao, A.Matsui, Y.YouLuTuz, S.Nagoshi, T.Uede, K.Fujiwara: "Increase expression of osteopontin in activated kupffer cells and hepatic macrophages during macrophage migration in Propionibacterium acnes-treated rat liver."J.Gastroenterol. 35(9). 743-749 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] N.Shijubo, T.Uede, S.Kon, M.Nagata, S.Abe: "Vascular endothelial growth factor and osteopontin in tumor biology."Crit.Rev.Oncog.. 11(2). 135-146 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] T.Takahashi, T.Tagami, S.Yamazaki, T.Uede, J.Shimizu, N.Sakaguchi, TW.Mak, S.Sakaguchi: "Immunologic self-tolerance maintained by CD25(+)CD4(+)regulatory T cells constitutively expressing cytotoxic T lymphocyte-associated antigen 4."J.Exp.Med.. 192(2). 203-310 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] S.Chiba, MM.Rashid, H.Okamoto, H.Shiraiwa, S.Kon, M.Maeda, M.Murakami, M.Inobe, A.Kitabatake, T.Uede: "The role of osteopontin in the development of granulomatous lesions in lung."Microbiol.Immunol.. 44(4). 319-332 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] S.Kon, M.Maeda, T.Segawa, Y.Hagiwara, Y.Horikoshi, S.Chikuma, K.Tanaka, MM.Rashid, M.Inobe, AF.Chambers, T.Uede: "Antibodies to different peptides in osteopontin reveal complexities in the various secreted forms."J.Cell.Biochem.. 77(3). 487-498 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Takemoto, K.Yokote, M.Nishimura, T.Shigematsu, T.Hasegawa, S.Kon, T.Uede, T.Matsumoto, Y.Saito, S.Mori: "Enhanced expression of osteopontin in human diabetic and analysis of its functional role in accelerated atherogenesis."Arterioscler. Throm.Vasc.Biol.. 20(3). 624-628 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] N.Shijubo, T.Uede, S.Kon, M.Maeda, T.Segawa, A.Imada, M.Hirasawa, S.Abe: "Vascular endothelial growth factor and osteopontin in stage I lung adenocarcinoma."Am.J.Respir.Crit.Care.Med.. 160(4). 1269-1273 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] T.Yasui, K.Fujita, Y.Hayashi, K.Ueda, S.Kon, M.Maeda, T.Uede, K.Kohri: "Quantification of osteopontin in the urine of healthy and stone-forming men."Urol.Res.. 27(4). 225-230 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] H.Hotta, S.Kon, YU.Katagiri, N.Tosa, T.Tsukamoto, AF.Chambers, T.Uede: "Detection of various epitopes of murines osteopontin by monoclonal antibodies."Biochem.Biophys.Res.Commun.. 257(1). 6-11 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] R.Kawashima, S.Mochida, A.Matsui, Y.YouLuTuz, K.Ishikawa, K.Toshima, F.Yamanobe, M.Inao, H.Ikeda, A.Ohno, S.Nagoshi, K.Fujiwara: "Expression of osteopontin in kupffer cells and hepatic macrophages and Stellate cells in rat liver after carbon tetrachloride intoxication : a possible factor for macrophage migration into hepatic necrotic areas."Biochem.Biophys.Res.Commun.. 256(3). 527-531 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] YU.Katagiri, J.Sleeman, H.Fujii, P.Herrich, H.Hotta, K.Tanaka, S.Chikuma, H.Yagita, K.Okumura, M.Murakami, I.Saiki, AF.Chambers, T.Uede: "CD44 variants but not CD44s cooperate with β1-containing integrins to permit cells to bind to osteopontin independently of arginine-glycine-aspartic acid, thereby stimulating cell motility and chemotaxis."Cancer Res.. 59(1). 219-226 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] J.Iizuka, Y.Katagiri, N.Tada, M.Murakami, T.Ikeda, M.Sato, K.Hirokawa, S.Okada, M.Hatano, T.Tokuhisa, T.Uede: "Introduction of an osteopontin gene confers the increase in B1 cell population and the production of anti-DNA autoantibodies."Lab.Invest.. 78(12). 1523-1533 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] K.Shigehara, N.Shijubo, M.Hirasawa, S.Abe, T.Uede: "Immunolocarization of extracellular matrix proteins and integrins in sarcoid lymph nodes."Virchows.Arch.. 433(1). 55-61 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] T.Fukumoto, N.Torigoe, S.Kawabata, M.Murakami, T.Uede, T.Nishi, Y.Ito, K.Sugimura: "Peptide mimics of the CTLA4-binding domains stimulate T-cell proliferation."Nat.Biotechnol.. 16(3). 267-270 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] T.Takahashi: "Immunologic self-tolerance maintained by CD25 (+) CD4 (+) regulatory T cells constitutively expressing cytotoxic T lymphocyte-associated antigen 4."J.Exp.Med.. 192(2). 303-310 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] N.Shijubo: "Vascular endothelial growth factor and osteopontin in tumor biology."Crit.Rev.Oncog.. 11(2). 135-146 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] S.Kon: "Antibodies to different peptides in osteopontin reveal complexities in the various secreted forms."J.Cell.Biochem.. 77(3). 487-498 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] S.Chikuma: "Janus kinase 2 is associated with a box 1-like motif and phosphorylates a critical tyrosine residue in the cytoplasmic region of cytotoxic associated molecule-4."J.Cell.Biochem.. 78(2). 241-250 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] S.Chiba: "The role of osteopontin in the development of granulomatous lesions in lung."Microbiol.Immunol.. 44(4). 319-332 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] M.Takemoto: "Enhanced expression of osteopontin in human diabetic and analysis of its functional role in accelerated atherogenesis."Arteriouscler.Thromb.Vasc.Biol.. 20(3). 624-628 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] N. Takemoto: "Enhanced expression of osteopontin in medial layer of forearm artery in patients with diabetes mellitus"Arterioscler. Thromb. Vas. Biol.. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] S. Kon: "Antibodies to different peptides in osteopontin reveal complexities in the various secreted forms"J. Cell. Biochem.. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] N. Shijubo: "Vascular andothelial growth factor and osteopontin in stage I lung adenocarcinoma"Am. J. Respir. Crit. Care. Med.. 160(4). 1269-1273 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Y. Katagiri: "CD44 variants but not CD44s cooperate with β1-containing integrins to permit cells to bind to osteopontin independently of arginine-glycine-aspartic acid, thereby stimulating cell motility and chemotaxis"Cancer Res.. 59(1). 219-226 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] T. Yasui: "Quantification of osteopontin in the urine of healthy and stone-forming men"Urol. Res.. 27(4). 225-230 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] H. Hotta: "Quantification of osteopontin in the urine of healthy and stone-forming men"Biochem. Biophys. Res. Commun.. 257(1). 6-11 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Iizuka,J.: "Introduction of an osteopontin gene confers the increase in B1 cell population and the production of anti-DNA autoantibodies." Lab.Invest.78. 1523-1533 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Katagiri,Y.: "CD44 variants but not CD44s cooperate with β1-containing integrins to permit cells to bind to osteopontin independently of BGD,thereby stimulating cell notility chemotaxis." Cancer Res.59. 219-226 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Shigehara,K.: "Immunolocalization of extracellular matrix proteins and integrins in sarcoid lymph nodes." Virchow's Archives. 433. 55-61 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Shijubo,N.: "Vascular endothelial growth factor and osteopontin in stage I lung adenocarcinoma." Am.J.Respir.Crit.Care.Med.(in press).

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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