1999 Fiscal Year Final Research Report Summary
Study of degradation mechanism of extracellular matrix in oral cancer and possible development of matrix metalloproteinase inhibitors as anticancer drugs
| Project/Area Number |
10470437
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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 | Kumamoto University |
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Principal Investigator |
SHINOHARA Masanori Kumamoto University School of Medicine Professor, 医学部, 教授 (90117127)
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| Co-Investigator(Kenkyū-buntansha) |
OHBAYASHI Takehisa Kumamoto University School of Medicine Assistant, 医学部, 助手 (80304997)
IKEBE Tetsuro Faculty of Dentistry, Kyushu University Assistant, 歯学部, 助手 (20202913)
NAKAMURA Seiji Faculty of Dentistry, Kyushu University Assistant Prof., 歯学部, 講師 (60189040)
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| Project Period (FY) |
1998 – 1999
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| Keywords | Squamous cell carcinoma / Invasion / Metastasis / MMP / TIMP |
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| Research Abstract |
(A) We studied the roles of MMP and TMP in metastastic mechanisms of oral squamous cell carcinoma. 1) When SCC cell lines were either cultured in vitro or transplanted in the tongue of nude mice, the metastatic cell lines tended to show a stronger expression of MMP-1, -2, -9 and MT-MMP than the non-metastatic cell lines. 2) The gelatinolytic activities in the homogenates were measured by gelatin zymography and its densitometric analysis. Highly metastatic cases showed the increased gelatinolytic activities of MMP-2 and MMP-9 in the tissue specimens of cell line and transplanted in the tongue of nude mice. These results therefore suggest that tumor progression is dependent on the ability of tumor cells to degrade extracellular matrix (ECMs), while the metastasis of tumors is regulated by many types of MMPs, and the overproduction of MMPs therefore appears to be more important for metastasis than the production of TIMPs in vivo.
(B) We studied possible development of matrix metalloproteinase inhibitors as anticancer drugs.
We divided nude mice which were transplanted SCC cell lines into two groups, anticancer drugs group : the groups of mice which were given anticancer drugs, control groups : the groups of mice which were not given anticancer drugs. 1) Tumors size of anticancer drug groups was smaller than control groups. In anticancer drug groups, cervical lymph metastasis were not found. 2) MMP and TIMP expression was examined in transplanted tumors. In anticancer drugs group, a lower expression of MMPs and TIMPs were recognized than in control groups.
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