| Project/Area Number |
09470451
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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 | Niigata University |
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Principal Investigator |
NAKAJIMA Tamio Niigata University Faculty of Dentistry Professor, 歯学部, 教授 (10014010)
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| Co-Investigator(Kenkyū-buntansha) |
SHINGAKI Susumu Niigata University Faculty of Dentistry Associate Professor, 歯学部, 助教授 (30134943)
ODA Kimimitsu Niigata University Faculty of Dentistry Professor, 歯学部, 教授 (10122681)
SAKU Takashi Niigata University Faculty of Dentistry Professor, 歯学部, 教授 (40145264)
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| Project Period (FY) |
1997 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥12,700,000 (Direct Cost: ¥12,700,000)
Fiscal Year 1999: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1998: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1997: ¥7,900,000 (Direct Cost: ¥7,900,000)
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| Keywords | oral carcinoma / lymph node metastasis / adhesion molecules / MMP / TIMP |
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| Research Abstract |
The mechanism of lymph node metastasis of oral carcinomas was studied using high and low metastatic O-IN cells, O-IN tumor tissues and human specimens. In light and electron microscopic studies, direct invasion of lymphatic and blood vessels by tumor nests was observed at sites with transplantation of O-IN cells and O-IN tumor tissues. Similar pattern of invasion was also observed in human specimens. Expressions of E-cadherin, λ and β catenins, α6 integrin and laminin were confirmed in the high and low metastatic cells. Their expressions were reduced in tumor nests in the periphery, but not in tumor nests about to penetrate vascular vessels, indicating that the reduced expressions of adhesion molecules are not necessarily indispensable for tumor metastasis. The possibility of early detection of micrometastasis in O-IN was suggested in RT-PCR of blood samples using cytokeratin 19. The enzyme activities of MMP3 and 9 were much higher in the metastatic cells than in the nonmetastatic cells. mRNAs of MMP2 and 3 and TIMP1 and 2 were also well expressed in the high metastatic cells and in O-IN tumor tissues. MMP9 was active in the metastatic tumor tissues, whereas the activities of TIMP1 and 2 were not detected or very low in the buccal and metastatic tumors, but definite evidence to substantiate the relationship between lymph node metastasis and their activities was not obtained. The effects of TNP-470, a specific inhibitor of angiogenesis, on lymph node metastasis are being studied in O-IN.
The results of the study indicated that the mechanism of lymph node metastasis of oral carcinomas is different from the one described in many articles on cancer metastasis.
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