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Anti-oral cancer strategy by means of inhibition of cellular adhesion to extracellula matrices

Research Project

Project/Area Number 10557170
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field 病態科学系歯学(含放射線系歯学)
Research InstitutionNIIGATA UNIVERSITY

Principal Investigator

SAKU Takashi  NIIGATA UNIVERSITY, Graduate School of Medical and Dental Sciences, Professor, 大学院・医歯学総合研究科, 教授 (40145264)

Co-Investigator(Kenkyū-buntansha) SUZUKI Makoto  NIIGATA UNIVERSITY, University Dental Hospital, Lecture, 歯学部・付属病院, 講師 (50107778)
IDA Hiroko (YONEMOCHI Hiroko)  NIIGATA UNIVERSITY, Graduate School of Medical and Dental Sciences, Assistant, 大学院・医歯学総合研究科, 助手 (60293213)
CHENG Jun  NIIGATA UNIVERSITY, Graduate School of Medical and Dental Sciences Associate, Professor, 大学院・医歯学総合研究科, 助教授 (40207460)
NAKAJIMA Motowo  NIIGATA UNIVERSITY, Novartis Pharma, Tsukuba Institute, Manager, 癌研究グループ, マネジャー(研究職)
OHSHIRO Kazufumi  NIIGATA UNIVERSITY, Graduate School of Medical and Dental Sciences, Assistant, 大学院・医歯学総合研究科, 助手 (50332648)
木村 信  新潟大学, 歯学部, 助手 (80251825)
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥13,700,000 (Direct Cost: ¥13,700,000)
Fiscal Year 2000: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1999: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1998: ¥9,600,000 (Direct Cost: ¥9,600,000)
Keywordsextracellular matrix / heparan sulfate proteoglycan / fibronectin / integrin / cell adhesion / focal adhesion kinase / ACC3 / anti-cancer strategy / スラミン / RT-PCR / 口腔癌 / RGDペプチド
Research Abstract

We have analyzed anti-cancer effect in a situation in which adhesion of oral carcinoma cells to extracellular matrices is inhibited. To this end, suramin, a polysulfonated naphthylurea, which has been used as an anti-trypanosoma reagent but has also known as an inhibitor of lysosomal heparanase, was used for inhibition of adhesion of oral carcinoma cells, such as ACC3 cells of human salivary adenoid cystic carcinoma origin.
ACC3 cells have been known to biosynthesize excessive amounts of extracellular matrix (ECM) molecules, especially basement membrane-associated molecules, such as heparan sulfate proteoglycan, HSPG/perlecan, and fibronectin. When ACCE cess were cultivated in the presence of 100 ;uM suramin, secretion of ECM molecules by ACC3 cells into the culture medium was enhanced. When 200 fM suramin was added, attachment of ACC3 cells to culture dishes reduced significantly. In the presence of suramin and RGD peptides, which are an ECM recoginition site of integrins, the attachme … More nt was two times more inhibited. Thus, it was suggested that suramin affected integrih-dependent cell adhesion. By day 7 of culture in the presence of suramin, ECM molecules were shed more prominently into the culture medium of ACC3 cells. Immunofluorescence showed that ECM molecules and integrins were localized within the cytoplasm but not in the extracellular space or in the cell surface. These results indicated suramin inhibited cell membrane assembly of integrin and consequently trapping of ECM molecules by cell surface integrins.
Immunoprecipitation and pulse-chase experi-ments showed that suramin inhibited biosynthesis of an unknown molecule with Mr. 120 kDa, which was co-precipitated with integrin a5. Immunoblotting experiments showed that the 120 kDa molecule was focal adhesion kinase (FAK), which functions in phospholylation of integrins. The results indicated that suramin inhibit FAK expression of ACC3 cells, which resulted in integrin function in cellular attachment.
These results clearly indicate that the inhibition of cell surface receptors for ECM molecules can be one of the strategies for suppression of oral carcinoma cell growth. Less

Report

(4 results)
  • 2001 Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (34 results)

All Other

All Publications (34 results)

  • [Publications] Ida-Yonemochi, H. et al.: "The basement membrane-type hepran sulfate proteoglycan (perlecan) in amelolastomas: its intercellular localization in stellate retlculum-like foci and biosynthesis by tumor cells in culture"Virchows Arch. DOI101007. S00428-001-0556-y (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sabit, H. et al.: "Enhanced expression of basement-membrane-type heparan sulfate proteoglycan in tumor fibro-myxoid stroma of intrahepatic cholangio-carcinoma"Pathology International. 51(4). 248-256 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kimura, S. et al.: "Perlecan (heparan sulfate proteoglycan) gene expression reflected in the characteristic histological architecture of salivary adenoid cystic carcinoma"Virchows Arch. 437(2). 122-128 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Murata, M. et al.: "Enamel protein s and extracellular matrix molecules are co-localized in the pseudocystic stroma space of adenomatoid odontogenic tumor"Journal of Oral Pathology & Medicine. 29(10). 483-490 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kimura, S. et al.: "Basement membrane heparan sulfate proteoglycan (perlecan) synthesized by ACC, adenoid cystic carcinoma cell of human salivary gland origin"Journal of Biochemistry. 25(2). 406-413 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Toyoshima, K. et al.: "High-molecular-weight fibronectin synthesized by adenoid cystic carcinoma cells of salivary gland origin"Japanese Journal of Cancer Research. 90(3). 308-319 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ida-Yonemochi H. et al.: "Xanthomatous lesion of the gingiva: a possible cause of delayed tooth eruption"Oral medicine & Pathology. 4(2). 79-84 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yonemochi, H. et al.: "Pericoronal hamartomayous lesions in the opercula of teeth delayed in eruption immunohistochemical study of the extracellular matrix"Journal of Oral Pathology & Medicine. 27(8). 441-452 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Irie, T. et al.: "Intracellular transport of basement membrane-type heparan sulfate proteoglycan in adenoid cystic carcinoma cells of salivary gland origin: an immunoelectron microscopic study"Virchows Arch. 433(1). 41-48 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ida-Yonemochi, H. et al: "The basement membrane-type hepran sulfate proteoglycan (perlecan) in amelolastomas: its intercellular localization in stellate reticulum-like foci and biosynthesis by tumor cells in culture"Virchows Arch DOI. 1007/s00428-001 0556-y. (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sabit H, et al: "Enhanced expression of basement-membrane-type heparan sulfate proteoglycan in tumor fibro-myxoid stroma of intrahepatic cholangio-carcinoma"Patholoay International. 51(4). 248-256 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kimura, S. et al: "Perlecan (heparan sulfate proteoglycan) gene expression reflected in the characteristic histological architecture of salivary adenoid cystic carcinoma"Virchows Arch. 437(2). 122-128 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Murata, M. et al: "Enamel protein s and extracellular matrix molecules are co-localized in the pseudpcystic stroma space of adenomatoid odontogenic tumor"Journal of Oral Pathology & Medicine. 29(10). 483-490 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kimura, S. et al: "Basement membrane heparan suifate proteoglycan (perlecan) synthesized by ACC, adenoid cystic carcinoma cell of human salivary gland origin"Journal of Biochemistry. 25(2). 406-413 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Toyoshima, K. et al: "High-molecularweight fibronectin Synthesized by adenoid cystic carcinoma cells of salivary gland origin"Japanese Journal of Cancer Research. 90(3). 308-319 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] lda-Yonemochi, H. et al: "Xanthomatous lesion of the gingiva: a possible cause of delayed tooth eruption"Oral Medicine & Pathology. 4(2). 79-84 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yonemochi, H. et al: "Pericoronal hamartomatous lesions in the opercula of teeth delayed in eruption: an immunohistochemical study of the extracellular matrix"Journal of Oral Pathology & Medicine. 27(8). 441-452 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Irie, T. et al: "lntracellular transport of basement membrane-type heparan sulfate proteoglycan in adenoid cystic carcinoma cells of salivary gland origin: an immunoelectron microscopic study"Virchows Arch. 433(1). 41-48 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kimura,S.: "Perlecan (heparan sulfate proteoglycan) gene expression reflected in the characteristic histological architecture of salivary adenoid cystic carcinoma."Virchows Arch. 437. 122-128 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Murata,M.: "Enamel protein s and extracellular matrix molecules are co-localized in the pseudocystic stroma space of adenomatoid odontogenic tumor."Journal of Oral Pathology & Medicine. 29. 483-490 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kimura,S.: "Basement membrane heparan sulfate proteoglycan (perlecan) synthesized by ACC, adenoid cystic carcinoma cell of human salivary gland origin."Journal of Biochemistry. 25. 406-413 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Toyoshima,K.: "High-molecular-weight fibronectin synthesized by adenoid cystic carcinoma cells of salivary gland origin."Japanese Journal of Cancer Research. 90. 308-319 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yonemochi,H.: "Immunohistochemical localization of extracellular matrix molecules in complex odontoma."Dentistry in Japan. 35. 13-19 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Irie,T.: "Intracellular transport of basement membrane-type heparan sulfate proteoglycan in adenoid cystic carcinoma cells of salivary gland origin : an immunoelectron microscopic study."Virchows Arch. 433. 41-48 (1998)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kimura, S. et al.: "Basement membrane heparan sulfate proteoglycan (perlecan) synthesized by ACC, adenoid cystic carcinoma cell of human salivary gland origin."Journal of Biochemistry. 25. 406-413 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Toyoshima, K. et al.: "High-molecular-weight fibronectin synthesized by adenoid cystic carcinoma cells of salivary gland origin."Japanese Journal of Cancer Research. 90. 308-319 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kimura, S. et al.: "Perlecan gene expression reflected in the characteristic histological architecture of salivary adenoid cystic carcinoma."Virchows Archiv. 45(印刷中). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] 木村 信 ほか: "腺様嚢胞癌由来ACC3細胞のライソゾーム系に対するスラミンの影響"歯科基礎医学会雑誌. 41. 471 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kimura,S.et al.: "Basement membrane heparan sulfate proteoglycan(perlecan)synthesized by ACC,adenoid cystic carcinoma cell of human salivary gland origin." Journal of Biochemistry. 25. 406-413 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Toyoshima,K.et al.: "High-molecular-weight fibronectin synthesized by adenoid cystic carcinoma cells of salivary gland origin." Japanese Journal of Cancer Research. 90. 308-319 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Irie,T.et al.: "Intracellular transport of basement membrane type heparan sulfate proteoglycan in adenoid cystic carcinoma cells of salivary gland origin:an immunoelectron microscopic study." Virchows Archiv. 433. 41-48 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Munakata,R.et al.: "Spindle cell carcinoma of the gingiva." Journal of Oral Pathology & Medicine. 27. 180-184 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yonemochi,H.et al.: "Pericoronal hamartomatous lesions in the opercula of teeth delayed in eruption:an immunohistochemical study of extracellar matrix." Journal of Oral Pathology & Medicine. 27. 441-452 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ono,Y.et al.: "Vascular invasion of O-1N,hamster squamous cell carcinoma with high potential of lymph node metastasis:Ultrastrucutural comparison between lymphatics and blood vessels." Pathology International. 48. 254-264 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2021-11-05  

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