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Development of a monoclonal antibody specific to cancer stroma and a basic study for the medical application

Research Project

Project/Area Number 09557018
Research Category

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

Allocation TypeSingle-year Grants
Section展開研究
Research Field Human pathology
Research InstitutionMie University

Principal Investigator

YOSIDA Toshimichi  Mie University, Faculty of Medicine, Professor, 医学部, 教授 (80166959)

Co-Investigator(Kenkyū-buntansha) SOTOYAMA Hiroshi  Fujita Health University School of Medicine, Lecturer, 医学部, 講師 (90247643)
MATSUMURA Kaname  Mie University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (70126994)
SAKAKURA Teruyo  Mie University, Faculty of Medicine Professor, 名誉教授 (80073120)
YOSHIDA Kyoko (IMANAKA,KYOKO)  Mie University, Faculty of Medicine, Lecturer, 医学部, 講師 (00242967)
Project Period (FY) 1997 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥11,500,000 (Direct Cost: ¥11,500,000)
Fiscal Year 2000: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1999: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1998: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1997: ¥5,500,000 (Direct Cost: ¥5,500,000)
KeywordsTenascin-C / Monoclonal antibody / Beast cancer / Cancer Stroma / Imaging / Extracellular matrix / がん / テネイシン / フィブロネクチン
Research Abstract

Tenascin-C and cellular fibronectin are known as onco-fetal extracellular matrix (ECM) proteins expressed in embryonic tissues and cancer stroma. These molecules are produced by mesenchymal and epithelial cells under such microenvironments, and deposits in the tissues in higher levels than in normal adult tissues. Furthermore, there are various splicing variants of these molecules, which seem to be exclusively expressed in cacer tissues. In this study, we explore specificities of cancer stroma, produce a monoclonal antibody specific to cancer stroma, and develop the applicable methods for cancer treatments. 1) First we studied specific expression of known ECM proteins in cancer stroma. 2) we attempted to produce monoclonal antibodies specific to cancer stroma by immunization of extracted proteins from the stroma. 3) we also tested whether, after injection of fluorescence-lableled antibody in tumor-bearing mice, the antibody was accumulated in cancer stroma. For 1, we found that deposition of TN-C and cellular FN produced by cancer cells themselves are relatively specific in cancer stroma, which may play important roles in cancer progression. 2) we produced new monoclonal antibodies against cancer stromal proteins, possibly FN and proteoglycan. 3) we produced high affinity-monoclonal antibodies against TN-C by immunization to TNC-null mice. After the injection, the antibody was exclusively accumulated in stroma of mouse mammary tumor. Furthermore, antibodies against a spliced site of TNC which is included in cancer stromal one but not in normal tissue, were produced. The antibody showed positive reaction to cancer stroma, but negative in normal tissues.

Report

(5 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (52 results)

All Other

All Publications (52 results)

  • [Publications] Yoshida,T., et al.: "Co-expression of tenascin and fibronectin in epithelial and stromal cells of benign lesions and ductal carcinomas in human breast tissues."J.Pathol.. 182. 421-428 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hasegawa,K., et al.: "Differential expression of tenascin-c and tenascin-x in human astrocytomas. Acta Neuropathol."Acta Neuropathol.. 93. 431-437 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ilunga,K., et al.: "Analysis of tenascin mRNA expression in the murine mammary gland form embryogenesis to carcinogenesis : an in situ hybridization study."Int.J.Dev.Biol.. 41. 569-563 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hanamura,N., et al.: "Expression of fibronectin and tenascin-C mRNAs by myofibroblasts, vascular cells and epithelial cells in human colon adenomas and carcinomas."Int.J.Cancer.. 73. 10-15 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] sagawau,H., et al.: "Expression and degradation of tenascin-C in human lung cancers."Brit.J.Cancer. 77. 98-102 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shen,X., et al.: "Changes in ovarian expression of tissue-type plasminogen activator and plasminogen activator inhibitor type-1 messenger ribonucleic acids during ovulation in rat."Endocri.J.. 44. 341-348. (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Toyama,H, et al.: "Characterization of neuronal damage by iomazenil binding and cerebral blood flow in an ischemic rat model."Ann.Nucl.Med.. 12. 267-273 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 松本英一 他: "乳癌におけるFibronectin isoformsの発現."乳癌基礎研究. 7. 42-47 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yoshida T. et al.: "Involvement of tenascin-C in migration and proliferation of laryngeal cancer cells."Virchow Arch.. 435. 496-500 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Mizutani,H., et al.: "Topical Tocoretinate inproved hypertrophic scar, skin sclerosis in systemic sclerosis and morphea."Jpn J Cancer Res. 90. 320-325 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 小坂良 他: "癌間質における特異的モノクローナル抗体の作製の試み"乳癌基礎研究. 8. 20-25 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tanaka M., et al.: "Clinikcal significance of tenascin-C expression in osteosarcoma : Tenascin promotes distant metastasis of osteosarcoma."Int.J.Mol.Med.. 5. 505-510 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Li TF., et al.: "Distribution of tenascin-X in different synovial samples and synobial membrane-like interface tissue from asepticl loosening of total hip replacement."Rhematol Int. 19. 177-183 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Noda N., et al.: "Expression of tenascin-C in stromal cells of the murine uterus during early pregnancy : Induction by interleukin-1 alpha, prostaglandin E2 and prostaglandin F2 alpha."Biol Reprod. 1713-1720 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Imanaka-Yoshida,K., et al.: "Vinculin, talin, integrin a6b1 and laminin can serve as components of attachment complex mediating contraction force transmission from cardiomyocytes to extracellular matrix."Cell Motil Cytoskel.. 42. 1-11 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yoshimura,E., et al: "Expression of tenascin-C and integrin a9 subunit in regeneration of rat nasal mucosa after chemical injury : Involvement in migration and proliferation of epithelial cells."Cell Biol. 111. 259-264 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yoshida, T., et al.: "Co-expression of tenascin and fibronectin in epithelial and stromal cells of benign lesions and ductal carcinoma in human breast tissues."J.Pathol.. 182. 421-428 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hasegawa, K., et al.: "Differential expression of tenascin-c and tenascin-x in human astrocytomas."Acta Neuropathol.. 93. 431-437 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ilunga, K., et al.: "Analysis of tenascin mRNA expression in the murine mammary gland form embryogenesis to carcinogenesis : an in situ hybridization study."Int. J.Dev. Biol.. 41. 569-563 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hanamura, N., et al.: "Expression of fibronectin and tenascin-C mRNAs by myofibroblasts, vascular cells and epithelial cells in human colon adenomas and carcinomas."Int. J.Cancer.. 73. 10-15 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] sagawau, H., et al.: "Expression and degradation of tenascin-C in human lung cancers."Brit. J.Cancer. 77. 98-102 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shen, X., et al.: "Changes in ovarian expression of tissue-type plasminogen activator and plasminogen activator inhibitor type-1 messenger ribonucleic acids during ovulation in rat."Endocri. J.. 44. 341-348 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Toyama, H, et al.: "Characterization of neuronal damage by iomazenil binding and cerebral blood flow in an ischemic rat model."Ann. Nucl. Med.. 12. 267-273 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Imanaka-Yoshida. K., et al.: "Vinculin, talin, integrin a6b1 and laminin can serve as components of attachment complex mediating contraction force transmission from cardiomyocytes to extracellular matrix."Cell Motil Cytoskel.. 42. 1-11 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yoshimura, E., et al.: "Expression of tenascin-C and integrin a9 subunit in regeneration of rat nasal mucosa after chemical injury : Involvement in migration and proliferation of epithelial cells."Histochem Cell Biol. 111. 259-264 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tuori A, et al.: "The expression of tenascin-X in developing and adlt rat and human eye."Histochem J. 31. 245-252 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yamada E., et al.: "Tocoretinate inhibited the contration of collgen gell matrices by human dermal fibroblasts with tenascin-C expression."J Dermatol Sci. 22. 45-53 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yoshida T., et al.: "Involvement of tenascin-C in migration and proliferation of laryngeal cancer cells."Virchow Arch.. 435. 496-500 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Mizutani, H., et al.: "Topical Tocoretinate inproved hypertrophic scar, skin sclerosis in systemic sclerosis and morphea."J Dermatol.. 26. 11-17 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Matsumoto, E., et al.: "Expression of Fibronectin Isoforms in Human Breast Tissue : Production of Extra Domain A+/Extra Domain B+ by Cancer Cells and Extra Domain A+ by Stromal Cells."Jpn J Cancer Res. 90. 320-325 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tanaka M., et al.: "Clinikcal significance of tenascin-C expression in osteosarcoma : Tenascin promotes distant metastasis of osteosarcoma. Int."J.Mol. Med.. 5. 505-510 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Li TF., et al.: "Distribution of tenascin-X in different synovial samples and synobial membrane-like interface tissue from asepticl loosening of total hip replacement."Rhematol Int. 19. 177-183 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Noda N., et. al.: "Expression of tenascin-C in stromal cells of the murine uterus during early pregnancy : Induction by interleukin-1 alpha, prostaglandin E2 and prostaglandin F2 alpha."Biol Reprod. 1713-1720

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tanaka M., et al.: "Clinikcal significance of tenascin-C expression in osteosar coma : Tenascin promotes distant metastasis of osteosar coma."Int.J.Mol.Med.. 5. 505-510 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Li TF.,Warris V.,: "Distribution of tenascin-X in different synovial samples and synobial membrane-like interface tissue from asepticl loosening of total hip replacement."Rhematol Int. 19. 177-183 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Noda N.,: "Expression of tenascin-C in stromal cells of the murine uterus during early pregnancy : Induction by interleukin-1 alpha.prostaglandin E2 and prostaglandin F2 alpha."Biol Reprod. 63. 1713-1720 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Mizutani,H et al.: "Topical Tocoretinate improved hypertrophic scar,skin sclerosis in systemic sclerosis and morphea"J Dermatol. 26. 11-17 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Matsumoto,E.et al.: "Expression of Fibronectin Isoforms in Human Breast Tissue : Production of Extra Domain A+/Extra Domain B+ by Cancer Cells and Extra Domain A+ by Stromal Cells"Jpn J Cancer Res. 90. 11-17 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yoshida T.et al.: "Involvement of tenascin-C migration and proliferation of laryngeal cancer cells"Virchow Arch. 435. 496-500 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tuori A.et al.: "The expression of tenascin-X in developing and adult rat and human eye"Histochem J. 31. 245-252 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yoshimura,E.et al: "Expression of tenascin-C and integrin a9 subunit in regeneration of rat nasal mucosa after chemical injury : Involvement in migration and proliferation of epithelial cells"Histochem Cell Biol. 111. 259-264 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kusagawa,H et al.: "Expression and degradation of tenascin-c in human lung cancers." Brit.J.Cancer. 77. 98-102 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tian,D-Y.et al.: "Overexpression of caltractin gene in tumor-in filtrating lymphocytes." Int.J.Oncol.13. 1135-1140 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Toyama,H et al.: "Characterization of neuronal damage by iomazenil binding and cerebral blood flow in an ischemic rat model." Ann.Nucl.Med.12. 267-273 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Mizutani,H.et al.: "Topical Tocoretinate inproved hypertrophic scar,skin sclerosis in systemic sclerosis and morphea." J Dermatol.26. 11-17 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yoshimura et al.: "Expression of tenascin-C and integrin α9 subunit in regeneration of rat nasal mucosa after chemical injury:Involvementin migration and proliferation of epithelial cells." Histochem Cell Biol. (in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Matsumoto,E.et al.: "Expression of Fibronectin Isoforms in Human Breast Tissue: Production of Extra Domain A^+/Extra Domain B^+ by Cancer Cells and Extra Domain A^+ by Stromal Cells." Jap J Cancer Res. (in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yoshida,T., Matsumoto,E., Hanamura,N., Ilunga,K., Katsuta,K.,Ishihara,A., and Sakakura,T.: "Co-expression of tenascin and fibronectin in epithelial and stromal cells of benign lesions and ductal carcinomas in human breasttissues." J.Pathol.182. 421-428 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Hasegawa,K., Yoshida,T., Matsumoto,K., Katsuta,K., Waga,S., and Sakakura,T.: "Differential expression of tenascin-c and tenascin-x in human astrocytomas." Acta Neuropathol.93. 431-437 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ilunga,K., Yoshida,T., Iriyama,K., and Sakakura,T.: "Analysis of tenascin mRNA expression in the murine mammary gland form embryogenesis to carcinogenesis:an in situ hybridization study." Int.J.Dev.Biol.41. 569-563 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Hanamura,N., Yoshida,T., Matsumoto,E., Kawarada,Y., and Sakakura,T.: "Expression of fibronectin and tenascin-C mRNAs by myofibroblasts,vascular cells and epithelial cells in human colon adenomas and carcinomas." Int.J.Cancer.73. 10-15 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kusagawa,H., Onoda,K., Namikawa,S., Yada,I., Okada,A., Yoshida,T., and Sakakura,T.: "Expression and degradation of tenascin-c in human lung cancers." Brit.J.Cancer.77. 98-102 (1998)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-11-11  

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