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THE ROLE OF PTHrP AND INTEGRIN BETA3 SUBUNIT IN THE DEVELOPMENT OF SKELETAL METASTASES

Research Project

Project/Area Number 07670246
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionKOBE UNIVERSITY SCHOOL OF MEDICINE

Principal Investigator

KITAZAWA Sohei  KOBE UNIVERSITY SCHOOL OF MEDICINE,2ND DEPARTMENT OF PATHOLOGY,ASSISTANT PROFESSOR, 医学部, 講師 (90186239)

Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1996: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1995: ¥1,700,000 (Direct Cost: ¥1,700,000)
Keywordsin situ hybridizatin / skeletal metastases / integrin / PTHrP / 悪性腫瘍
Research Abstract

We have shown presice histological localization of parathyroid hormone-related protein (PTHrP) and alphavbeta3 integrin, a receptor for the osteopontine, by pathological technique. In a series of the clinico-pathological studies, we showed that the expression of the alphavbeta3 integrin, especially beta3 integrin subunit might play an important role in the definition of the tissue specificity. Futhermore, in other series of studies using surgical and autopsy specimens, we showed that the tumor-derived PTHrP served to help the osteoblastic cell to generate the osteoclasts. As a result, PTHrP producing tumor-bearing host had a greater risk to have a eroded bone surface. The osteopontine, one of the major bone-residing bone matrix proteins, is, therfore, present at the site of roded bone surface. It is this ostopontine that the alphavbeta3 integrin is bond to. Taken together, tumor cell expressing PTHrP and alphavbeta3 integrin can have a better chance to attach and survive in a microenviroment of the bone.
During performing these histopathological studies, more sensitive and specific method for in situ hybridization was neccessory. While confirming our histomorphological data by biochemical studies as RT-PCR,we have developed highly sensitive in situ hybridization system using a bromodeoxyuridine as a hapten. We have presented our data at various international congress as well as domestic meetings, and publish a lot of scientific papaers for academic jurnals.

Report

(3 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] Riko Kitazawa: "In situ detection of parathyroid hormone-related profein (PTHrP) in ovarian clear cell carcinoma" Human Phthology. 28 (3). 379-382 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Morito Sakaue: "Molecular cloning and characterization of human bone morphogenic protein (BMP)-5 gene pronpter" Biochemiocal and Biohysical Research Communications. 22 (3). 768-772 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Liapis Helen: "Integrin α_Vβ_3 expression by bone-residing breast cancer metastases" Diagnostic Molecular Pathology. 5 (2). 127-135 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Sohei Kitazawa: "Development of skeketal metastases" Clinical Orthopedics and Related Research. 312. 45-50 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Sohei Kitazawa: "Interleukin-4 Induces expression of the integrin α_Vβ_3 via transactivation of the β_3l gene" The Journal of Biological Chemistry. 270. 4115-4120 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Yuka Idei: "Ovarian small cell carcinoma with k-ras mutation"

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Human Phthology. 27 (1). 77-79 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 北澤荘平: "組織細胞化学1996" 学際企画, 305 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kitazawa S., Maeda S.: "Development of skeletal metastases." Clinical Orthopaedics and Related Research.312. 45-50 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kitazawa S., Ross FP., McHugh K., Teitelbaum SL.: "Interleukin-4 Induces expression of the integrin alphavbeta3 via transactivation of the beta3 Gene." The Journal of Biological Chemistry.270 (8). 4115-4120 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Liapis H., Flath A., Katazawa S.: "Integrin alpha beta3 Expression by Bone-residing Breast Canser Metastases" Diagnostic Molecular Pathology. 5. 127-135 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Ishido S., Sakaue M., Asaka K., Maeda S.: "Detection of transforming growth factor-beta1 in coxsackie B3 virus-induced murine myocarditis." Acta Histochem. Cytochem.28 (2). 137-142 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Sakaue M., Kitazawa S., Nishida K., Kitazawa R., Maeda S.: "Molecular cloning and characterization of human bone morphogenic protein (BMP)-5 gene promoter." Biochemical and Biophysical Research Communications. 221 (3). 768-772 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Fujioka M., Shimada K., Kitazawa S., Maeda S.: "Molecular characterization of a novel cancer cell line established from human carcinoma in pleomorphic adenoma (CaPA-4)." The International Journal of Cancer.67. 204-210 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Idei Y., Kitazawa S., Fujimori T., Ajiki T., Asaka K., Takeuchi S., Mochizuki M., Chiba T., Maeda S.: "Ovarian Small Cell Ca with KRAS Mutation : A Case Report with Genetic Analysis" Human Pathology. 27. 77-79 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Fukunishi H., Murata K., Takeuchi S., Kitazawa S.: "Ovarian fibromatosis with minor sex cord elements" Archives of Gynecology and Obstetrics. 258. 207-211 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T Ajiki, T Fujimori, H Onoyama, M Yamamoto, S Kitazawa, S Maeda, Y Saitoh.: "K-ras gene mutation in gall bladder carcinomas and dysplasia." Gut. 38. 426-429 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Riko Kitazawa: "In situ demonstration of parathyroid hormone-related protein (PTHrP) mRNA in human normal parathyroid and secondary hyperplasia" Histochemistry and Cytochemistry. 777-778 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Sohei Kitazawa: "In situ demonstration of integrin β_3 Subunit mRNA in murine bone marrow macrophages" Histochemistry and Cytochemistry. 206-207 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Riko Kitazawa: "In situ detection of parathyroid hormone-related protein (PTHrP) in orarian clear cell carcinoma" Human Pathology. 28(3). 379-382 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Morito Sakaue: "Molecular cloning and characterization of human bone marphogenic protein (BMP)-5 gene promoter" Biochemical and Brophysical Research Communications. 221(3). 768-772 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Liapis Helen: "Integrin αvβ_3 expression by bone-residing breast canser metastases" Diagnostic Molecular Pathology. 5(2). 127-135 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Hidenobu Fukunishi: "Ovarian fibromotosis with minor sex cord elements" Archives of Gynecology and Obstetrics. 258. 213-218 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 北澤荘平: "組織細胞化学1996" 学際企画, 365 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] S. Kitazawa et al: "Development of Skeletal Metastases" Clinical Orthopaedics & Related Research. 312. 45-50 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] S. Kitazawa et al: "Interleukin-4 Induces Expression of the Integrin αvβ3 via Transactivation of the β_3 Gene" The Journal of Biological Chemistry. 270. 4115-4120 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Y. Idei et al: "Ovarian Small Cell Carcinoma with k-ras Mutation" Human Pathology. 27. 77-79 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] S. Kitazawa et al: "Clinico pathological Relevance of Parathyroid Hormone-related Protein in Various Types of Cancer tissues" Journal of Bone and Mineral Metabolism. 12. 145-151 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] H. Fukunishi et al: "Immunohistochemical Study on the Expression of Parathyroid Hormone-related Protein in Ovarian Tumors" Journal of Bone and Mineral Metabolism. 12. 153-155 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] M. Fujioka et al: "Molecular Characterization of a Novel Cancer Cell Line Established from Human Carcinoma in Pleomorphic Adenomd (CaPA-4)" International Journal of Cancer. (in press). (1996)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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