1997 Fiscal Year Final Research Report Summary
Role of the matrix-degrading enzymes and their inhibitors on invasion and metastasis of oral SCC
| Project/Area Number |
08672315
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | The University of Tokushima |
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Principal Investigator |
KAWAMATA Hitoshi The University of Tokushima, School of Dentistry Research Associate, 歯学部, 助手 (70224847)
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| Project Period (FY) |
1996 – 1997
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| Keywords | oral SCC / invasion / metastasis / Cytokeratin 20 / Tumor marker / matrix-degrading enzymes / TSC-22 / Transfection |
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| 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.
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