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The total analyses of the mechanism of the invasion and metastasis in human oral squamus cell carcinoma by the transcriptional factors

Research Project

Project/Area Number 11671994
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Surgical dentistry
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

MORIFUJI Masayo  University Dental Hospital, KYUSHU UNIVERSITY, assistant professor, 歯学部・附属病院, 助手 (90271113)

Co-Investigator(Kenkyū-buntansha) NAKABEPPU Yusaku  Medical Institute Bioregulation, KYUSHU UNIVERSITY, professor, 生体防御医学研究所, 教授 (30180350)
OHISHI Masamichi  Faculty of Dental Science, KYUSHU UNIVERSITY, professor, 歯学研究院, 教授 (70037505)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2000: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1999: ¥3,000,000 (Direct Cost: ¥3,000,000)
Keywordssquamous cell carcinoma / invasion and metastasis / transcriptional factors / growth factor / cytokine / transcriptional activity / MMP / orthotopic implantation / 細胞骨格 / 浸潤転移 / 接着分子 / VEGF
Research Abstract

The various invasive and metastatic genes have the common transcriptional factors such as AP-1, AP-2, SP-1 or NF-Kappa B.In our study, We investigated the relationship between these transcriptional activities and the abilities of invasion and metastasis. In this study, we used our SQUU cell lines derived from human oral squamous cell carcinoma. (When transplanted orthotopically, SQUU-A exhibited an expansive growth without either intravasation or cervical lymph nodemetastasis (0/13), while SQUU-B invaded the muscle with intravasation and cervical lymph node metastasis (86.7%, 13/15).).
Although In vitro migration assay showed the differences in the invasive ability between both unstimulated cell lines. In these cell lines, the transcriptional activities of AP-1, AP-2, SP-1 were detected, while that of NF-Kappa B was not. We stimulated these cell lines by growth factors (TNF-α, HGF, TGF-α, TGF-β, bFGF) and cytokines (IL-1 α, IL-1 β, IL-8, IL-12), respectively. TGF-α gave these cell lines … More the highest ability of invasion among the growth factors and cytokines. That of non metastatic cell line was 0.93%, while that of metastatic cell line was 48.4%. The metastatic cell line got much higher ability of invasion. Interestingly, in the metastatic cell line, the transcriptional activity of AP-1, Which regulates matrix metaloproteinase (MMP), increased by various growth factors and cytokines. In addition, the active type of MMP-2 was detected in the metastatic cell lines by stimulation, while not in non metastatic cell line. By TGF-β, the metastatic cell line had the up-regulation of MMP-2 and the transcriptional activity of AP-2 which regulates MMP-2. That suggests that the increase of transcriptional activity of AP-1or AP-2 may result in the up-regulation of MMP and active MMP, and may cause the acquisition of invasive ability in the metastatic cell line. But this is the insufficient explanation about the mechanism of invasion, because both cell lines had the transcriptional activities of AP-1 and AP-2, and the different invasive ability even by unstimulation. TNF-α, IL-1α, IL-1β made both cell lines increase of MMP-9 and caused the transcriptional activity of NF-Kappa B.There were no differences between both cell lines. Therefore, we are necessarily investigating another transcriptional factors. Less

Report

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

    (4 results)

All Other

All Publications (4 results)

  • [Publications] M.Morifuji,S.Taniguchi,H.Sakai,Y.Nakabeppu,M.Ohishi,: "Differential expression of cytokeratin after orthotopic implantation of newly establishedhuman tongue cancer cell lines of defined metastatic ability."Am.J.Pathol.. 156. 1317-1326 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Morifuji, S.Taniguchi, H.Sakai, Y.Nakabeppu, M.Ohishi: "Differential expression of cytokeratin after orthotopic implantation of newly established human tongue cancer cell lines of defined metastatic ability."Am.J.Pathol.. 156. 1317-1326 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Morifuji,S.Taniguchi,H.Sakai,Y.Nakabeoou,M.Ohishi.: "Differentialexpression of cytokeratin after orthotopic implantation of newly establishedhuman tongue cancer cell lines of defined metastatic ability."Am.J.Pathol.. 156. 1317-1326 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Masayo Morifuji,Shun'ichro Taniguchi,Hidetaka Sakai,Yusaku Nakabeppu,Masamichi Ohishi: "Differential expression of cytokeratin after orthotopic implantation of newly established human tongue cancer cell lines of defined metastatic ability"Amerucan Journal of Pathology. 154(4)april(in press). (2000)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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