The Membrane-Anchored Matrix Metalloproteinase Regulator RECK in Combination with MMP-9 as a novel prognostic indicator for digestive cancer.
| Project/Area Number |
16591342
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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 | Nara Medical University |
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Principal Investigator |
HISANAGA Michiyoshi Nara Medical University, Department of Surgery, Associate professor, 医学部, 助教授 (30275341)
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| Co-Investigator(Kenkyū-buntansha) |
NAGAO Mitsuo Nara Medical University, Department of Surgery, Assistant professor, 医学部, 助手 (10326340)
池田 直也 奈良県立三室病院, 外科, 医長 (20336861)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2005: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | RECK / MMP-9 / colorectal cancer / VEGF / micro vascular density / 大腸癌 |
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| Research Abstract |
RECK, a membrane-anchored regulator of matrix metalloproteinases (MMPs), is widely expressed in healthy tissue, whereas it is expressed at lower levels in many tumor-derived cell lines. Studies in mice and cultured cells have shown that restoration of RECK expression inhibits tumor invasion, metastasis, and angiogenesis. However, the clinical relevance of these findings remains to be fully documented. Here we examined the expression of RECK and one of its targets, MMP-9, in colorectal cancer tissue.
The RECK and MMP-9 expression levels in colorectal cancer samples from 53 patients were determined by immunohistochemical techniques. The expression level of each protein was scored, and the patients were devided into two groups based on these scores. In 33 cases, we performed gelatin zymography to estimate the degree of MMP-2 and MMP-9 activation. Microvessel density and vascular endothelial growth factor (VEGF) expression were also evaluated histologically/
RECK protein was detected in 30 of 53 (56.6%) specimens. Importantly, patients with tumors expressing relatively high levels of RECK (high-RECK group) had a significantly lower risk of recurrence than did patients with tumors expressing relatively low levels of RECK (low-RECK group ; P=0.011). Moreover, RECK-dominant (RECK score≧MMP-9 score) patients showed a significantly lower incidence of recurrence than did MMP-9 dominant patients (P=0.0003). Multivariate analysis revealed that the RECL/MMP-9 balance was an independent prognostic factor (P=0.0122). The expression of VEGF and microvessel density were inversely correlated with the level of RECK expression.
The results led us to conclude that RECK/MMP-9 balance is an informative prognostic indicator for colorectal cancer. Our data also suggest that RECK suppresses tumor angiogenesis, probably by limiting the availability of VEGF in tunor tissues.
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Report
(3 results)
Research Products
(3 results)
