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Human macrophage metalloelastase gene expression in colorectal carcinoma and its clinicopathologic significance
W Yang1, S Arii, M J Gorrin-Rivas
1Department of Surgery and Surgical Basic Science, Graduate School of Medicine, Kyoto University, Kyoto, Japan. weigeyang@hotmail.com
Background:
Human macrophage metalloelastase (HME), also referred as matrix metalloproteinase 12, has been shown to convert plasminogen into angiostatin, an essential inhibitor of tumor angiogenesis. The current study was designed to investigate the association of HME mRNA expression with disease progression of in patients with colorectal carcinoma.
Methods:
The expression of HME mRNA was quantified by Northern blot analysis in tumorous (T) and nontumorous (N) tissues obtained from 54 patients with primary colorectal carcinoma, and the ratio of these two tissue types was defined as the HME T/N ratio. The prognostic significance of this ratio after surgery, along with its correlation with disease progression and metastatic potential, was evaluated. The tissues also were subjected to in situ hybridization analysis for HME. The microvessel count after immunohistochemical staining of factor VIII was used to assess angiogenesis.
Results:
The HME T/N ratio showed an inverse correlation with the depth of the intestinal wall invasion, the lymphatic invasion, and the vascular invasion. The patients with overexpression of HME mRNA (HME T/N ratio > 1.191) significantly demonstrated better survival compared with those patients who did not show overexpression of HME mRNA. In situ hybridization identified the colorectal carcinoma cells as mainly responsible for the signal shown in Northern blot analysis. A considerable but not statistically significant lower microvessel density (MVD) was observed in the patients with HME overexpression.
Conclusions:
These findings demonstrate that the HME gene plays an important role in the inhibition of tumor progression in patients with colorectal carcinoma and that its overexpression is correlated closely with a better prognosis.
Insights
Overexpression of human macrophage metalloelastase (HME) mRNA in colorectal tumors correlates with reduced invasion and better patient survival. This suggests HME is a key inhibitor of colorectal cancer progression.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Human macrophage metalloelastase (HME), also known as matrix metalloproteinase 12, plays a role in converting plasminogen to angiostatin, a tumor angiogenesis inhibitor.
- Understanding HME's role in colorectal carcinoma is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the association between HME mRNA expression and disease progression in colorectal carcinoma patients.
- To evaluate the prognostic significance of HME mRNA expression after surgical resection.
Main Methods:
- HME mRNA expression quantified by Northern blot analysis in tumorous (T) and nontumorous (N) tissues from 54 colorectal carcinoma patients.
- HME T/N ratio calculated to assess expression levels.
- In situ hybridization used to localize HME expression.
- Microvessel density assessed via immunohistochemical staining for factor VIII to evaluate angiogenesis.
Main Results:
- HME T/N ratio inversely correlated with tumor invasion depth, lymphatic invasion, and vascular invasion.
- Patients with HME mRNA overexpression (T/N ratio > 1.191) showed significantly better survival rates.
- Colorectal carcinoma cells identified as the primary source of HME mRNA signal.
- A trend towards lower microvessel density observed in patients with HME overexpression, though not statistically significant.
Conclusions:
- HME gene expression is significantly associated with a better prognosis in colorectal carcinoma patients.
- HME overexpression plays a critical role in inhibiting tumor progression and metastasis in colorectal cancer.