1999 Fiscal Year Final Research Report Summary
The involvement of matrix metalloproteinase (MMP-7) in invasion and metastasis of gastrointestinal carcinoma.
| Project/Area Number |
10671198
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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 |
Digestive surgery
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
YOSHIKAWA Yasuji Medical institute of Bioregulation Kyushu Univ. Assistant Professor, 生体防御医学研究所, 助教授 (80124816)
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| Co-Investigator(Kenkyū-buntansha) |
SHIBUTA Kenji Medical institute of Bioregulation Kyushu Univ. Research associate, 生体防御医学研究所, 助手 (70253531)
SADANAGA Noriaki Medical institute of Bioregulation Kyushu Univ. Research associate, 生体防御医学研究所, 助手 (20304826)
MORI Masaki Medical institute of Bioregulation Kyushu Univ. Professor, 生体防御医学研究所, 教授 (70190999)
UTSUNOMIYA Tohru Medical institute of Bioregulation Kyushu Univ. Research associate, 生体防御医学研究所, 助手 (30304801)
HATAKENAKA Masamitsu Medical institute of Bioregulation Kyushu Univ. Research associate, 生体防御医学研究所, 助手 (40253413)
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| Project Period (FY) |
1998 – 1999
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| Keywords | Esophageal carcinoma / MMP-7 / cell cycle / G1 / S phase / cyclin D1 / p27 / c-myc |
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| Research Abstract |
We have investigated the expression of MMP-7 in gastrointestinal carcinomas. In colon carcinoma, MMP-7 expression was correlated with the clinical stage (Mori et al. 1995 Cancer) and in gastric carcinoma, it was significantly correlated with lymph node metastasis and lymphatic and vascular permeation (Honda et al. 1996 Gut). Now we analyzed 48 esophageal carcinoma patients regarding MMP-7 expression and revealed MMP-7 to be significantly correlated with lymph node metastasis and patient prognosis. In multivariate analysis regarding the prognosis, MMP-7 was a prognostic factor independetly of classical clinicopathological factor (p=0.0005) (Yamashita et al. Clin. Cancer Res. in press). MMP-7 was reported to be expressed in carcinoma cells of esophageal carcinoma tissues and our immunohistochemical results regarding esophageal carcinoma revealed MMP-7 protein to be expressed in carcinoma cells themselves as well. However, no esophageal carcinoma cell line in 13 was recognized to express MMP-7 mRNA expression, which showed the discrepancy of MMP-7 expression. This suggested MMP-7 expression to be induced by the carcinoma-host interaction. Therefore we transfected MMP-7 cDNA into KYSE150 (KY-7), which does not constitutively express MMP-7, and compared it with the parent cells (KY-P) to reveal their differences. KY-7 overexpressed cyclin D1 and c-myc and downregulated p27 protein after confluent state compared with KY-P and showed an increased uptake of BrdU, which suggested KY-7 to augment the proliferative capacity of cells. Both lines also showed the great difference of growth rate especially in dense concentration of cells. While MMP-u was known to be involved in tumorigenesis, but our result revealed a novel mechanism of involvement in tumorigenesis by MMP-7.
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