| Project/Area Number |
10470432
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Surgical dentistry
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| Research Institution | Osaka University |
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Principal Investigator |
NAKAZAWA Mitsuhiro Fac. of Dent., Osaka Univ. Hospital Reseach Assistant, 歯学部・附属病院, 講師 (70217701)
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| Co-Investigator(Kenkyū-buntansha) |
TAMURA Hiroshi Fac. of Dent., Osaka Univ. Hospital Senior resident, 歯学部・附属病院, 医員
IWAI Soichi Fac. of Dent., Osaka Univ. Hospital Senior resident, 歯学部・附属病院, 医員
KATO Itsuro Fac. of Dent., Osaka Univ. Hospital Reseach Assistant, 歯学部・附属病院, 助手 (60314390)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥12,900,000 (Direct Cost: ¥12,900,000)
Fiscal Year 1999: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 1998: ¥9,500,000 (Direct Cost: ¥9,500,000)
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| Keywords | Squamous cell carcinoma / Tumor-fibroblasts interaction / E-Cadherin / HGF / invasion / Squamous cell carcinoma / Tumor-fibroblasts interaction / E-Cadherin / HGF / invasion / squamous cell carcinoma |
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| Research Abstract |
To examine the mechanisms of invasive potential in oral squamous cell carcinomas (OSCC), we investigated characteristics of tumor biology, especially focused on tumor-stromal interaction, using two established human cancer cell lines, IF cell (high malignancy) and HOSO cell (low malignancy) from 0SCC patients. The results are as follows. (1) The animal model using nude mice reproduced almost same histopathological findings and conditions of disease as those in the patients. (2) IF cell produced Transforming growth factor (TGF) -α and TGF-β1 as autocrine cell motility factors, however HOSO cell produced nothing. (3) IF cell produced factors which reduced the expression of E-cadherin/α-catenin. One of the factors seemed to be a HGF (humoral factor) produced by fibroblast (Fb) because IF cell cocultured with Fb, inhibited cell-cell contact without direct contact to Fb. But HOSO cell did not. (4) The results of experiments using matrigel and collagen gel matrix revealed that on e of important cell invasion factors was not TGF-α and TGF-β1 but HGF because TGF-α or TGF-β1 added groups showed non- invasive cystic structure, however Fb-conditioned media (CM) or HGF added group showed invasive structure. Invasive potential of IF cell was about 4 times potent than that of HOSO. (5) Both IF and HOSO cell produced Interleukin -1 (IL-1) as paracrine HGF-inducer. But the amount of IL-1 produced by IF was about 3 times more than that of HOSO. (6) G-CSF、 TGF-α were produced by IF as autocrine growth factors, but HGF was prduced by Fb as an paracrine growth factor. TGF-β showed inhibitory growth factor of IF. These results indicate that high malinant IF cell interacts with host-fibroblast more strongly than low malignant HOSO do. Utilization of multiple factors which influence cell motility, invasiveness, proliferation and cell adhesion molecules, that act in autocrine and paracrine pathways may confer highly invasive and proliferation potentials at the microenvironment.
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