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Role of the matrix-degrading enzymes and their inhibitors on invasion and metastasis of oral SCC

Research Project

Project/Area Number 08672315
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Surgical dentistry
Research InstitutionThe University of Tokushima

Principal Investigator

KAWAMATA Hitoshi  The University of Tokushima, School of Dentistry Research Associate, 歯学部, 助手 (70224847)

Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1997: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1996: ¥1,600,000 (Direct Cost: ¥1,600,000)
Keywordsoral SCC / invasion / metastasis / Cytokeratin 20 / Tumor marker / matrix-degrading enzymes / TSC-22 / Transfection / 転移 / マイクロダイセリション / ザイモグラフィ / サイトケラチン / RT-PCR
Research Abstract

We examined the expression of gelatinases and their inhibitors in human oral SCC cells, BHY (non-metastatic) and HN (metastatic). Both of the cells expressed several gelatinases. In addition, BHY cells secreted proMMP7 and procathepsin L,while HN cells secreted a large amount of active MMP2. HN cells secreted TIMP1, but only a trace level of TIMP2. The net activity of MMP2 and cathepsin L secreted from cancer cells may contribute respective to lymph node metastasis and the bone invasion of oral cancer cells.
We examined the gelatinases in human oral SCC tissues by a microdissection-zymography. The gelatinolytic activities in cancer cell nests were much higher than those of normal gingival epithelium. The activities of active-MMP2 in cancer cell nests of metastatic cancers were significantly higher than those of non-metastatic cancers (p<0.05). We also examined the existence of circulating cancer cells in the peripheral blood of oral SCC patients by RT-PCR for cytokeratin 20 (CK20) mRNA.Eleven of 12 oral SCC patients showed positive results. However, there is no clear relationship of hematogenous CK20 mRNA for metastasis. All of the tumor-free survivors showed negative results. The expression of active-MMP2 in cancer cells can be used as a predictive marker for metastasis, and CK20 mRNA in peripheral blood can be used as a marker for tumor-recurrence in oral SCC patients.
We isolated a growth suppressor gene, TSC-22. Then we analyzed the role of the gene on metastatic potentials of oral cancers. However, transfection of either sense or antisense TSC-22 gene did not affect the metastatic potentials of TYS cells. Futhermore, there was no significant difference in the expression of TSC-22 mRNA between metastatic oral cancers and none-metastatic oral cancers.

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] Kawamata et al.: "possible contribution of active MMP2 to lymph-nate mefastasis and secreatcl cattiepsin Ltoboue invasion of uewly estadlished oral squamaus caucer cell lines." International Journal of Cancer. 70・1. 120-127 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Tanaka et al.: "Angiogenesis mhibitor TNP-470 suppresses tumorigenesis in rat urinany blodder." Journal of Urology. 157・2. 683-688 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kawamata et al.: "Induction of TSc-22 by Treatment with a new anti-cancer drug,resnarinone,in a human salivary gland cellcer." British Journal of Cancer. 77・1. 71-78 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nakashiro et al.: "Down-regulation of TSc-22(TGF-B stimulatecl clone-22)markedly enhances the growth of a human salivany gland caucer cell like invitro and invivo." Cancer Research. 58・3. 549-555 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kawamata et al.: "Active MMP2 expression and homatogeneous Cytokeratin 20 mRNA as a predictive marker for netastasis and recurrence in oral cancer pationt" British Journal of Cancer. (in press). (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kawamata H,Nakashiro K,Uchida D,Harada K,Yoshida H,and Sato M: "Possible contribution of active MMP2 to lymphnode metastasis and secreted cathepsin L to bone invasion of newly established human oral-squamous-cancer cell lines." Int J Cancer.70 (1). 120-127 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Tanaka Y,Kawamata H,Fujimoto K and Oyasu R: "Angiogenesis inhibitor TNP-470 suppresses tumorigenesis in rat urinary bladder." J Urol.157 (2). 683-688 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kawamata H,Nakashiro K,Uchida D,Hino S., Omotehara F,Yoshida H and Sato M: "Induction of TSC-22 by treatment with a new anti-cancer drug Vesnarinone in a human salivary gland cancer cell." British J Cancer. 77 (1). 71-78 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nakashiro K,Kawamata H,Hino S,Uchida D,Miwa Y,Hamano H,Omotehara F,Yoshida H and Sato M: "Down-regulation of TSC-22 (TGF-beta stimulated clone-22) markedly enhances the growth of a human salivary gland cancer cell line in vitro and in vivo." Cancer Res.58 (3). 549-555 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kawamata H,Uchida D,Hamano H,Kimura-Yanagawa T,Nakashiro K,Hino S,Omotehara F,Yoshida H and Sato M: "Active MMP2 expression and hematogeneous cytokeratin 20 mRNA as a predictive marker for metastasis and recurrence in oral cancer patients." British J Cancer. (in press). (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kawamata et al.: "Possible contribution of active MMP2 to lymph-nade metastasis and secreated cathepsin L to bone Invasion of heusly established oral squamous cancer cell lines." International Journal of Cancer. 70・1. 120-127 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tanaka et al.: "Angiogenesis inhibitor TNP-470 suppresses tumorigenesis in rat urinary bladder" Journal of Urology. 157・2. 683-688 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kawamata et al.: "Induction of TSC-22 by treatment with a new anti-cancer drug,vesnarinone,In a human salivary gland cancer" British Journal of Cancer. 77・1. 71-78 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Nakashiro et al.: "Down-regulation of TSC-22(TGP-β stimulated clone-22)markedly enhances the growth of a human solivary gland cancer cell line invitro and invivo" Cancer Research. 58・3. 549-555 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kawamata et al.: "Active MMP2 expression and hematogeneous cytokeratin 20 mRNA as a prodictive marker for metastasis and recurrence inoral cancer patients." British Journal of Cencer. (in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Hitoshi kawawata,kohichi Nakashiro Daisuke Uchida,Kaji Harada,Hieo Yoshida,Mitsunobu Sato: "Possible Contrihution of Active MMP2 to Lymph-nodc mctastasis and Secreted Cathepsln L to bone lnvasion of hewly established human oral squamaus Cancer coll line" International Journal of Cancer. 70(1). 120-127 (1997)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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