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Membrane-type 1 matrix metalloproteinase mRNA expression in colorectal cancer
T C Sardinha1, J J Nogueras, H Xiong
1Department of Colorectal Surgery, Cleveland Clinic Florida, Fort Lauderdale 33309, USA.
Purpose:
Membrane-type matrix metalloproteinases are recently described proteolytic enzymes belonging to the matrix metalloproteinase family. Initial studies have indicated that membrane-type matrix metalloproteinases are involved in tumor invasion and metastasis. Membrane-type 1 matrix metalloproteinase is the first membrane-type matrix metalloproteinase to be described. The aim of this study was to investigate the expression of membrane-type 1 matrix metalloproteinase mRNA in colorectal cancer.
Methods:
Samples were collected from surgical specimens of patients with colorectal adenocarcinoma and were immediately frozen in liquid nitrogen and stored at -80 degrees C until processed. Both normal and cancer tissue was taken from each patient. TNM stage, tumor differentiation, mucin production, and vascular invasion were assessed. Northern blotting was used to quantify membrane-type 1 matrix metalloproteinase mRNA levels in the samples using a membrane-type 1 matrix metalloproteinase cDNA clone. X-ray film images were digitized and densitometry was used to quantify bands. All samples were normalized against 18S rRNA levels. Results are expressed as the ratio of cancer to normal tissue levels. Statistical analysis was performed using analysis of variance, with P < 0.05 accepted as the level of significance.
Results:
A total of 32 samples were prospectively analyzed. The correlation between TNM stage and increased expression of membrane-type 1 matrix metalloproteinase mRNA in cancer tissue over normal tissue is expressed in the mean ratio of cancer to normal tissue expression for Stages I through IV, respectively: 1.4 +/- 0.2 (12 patients); 4.1 +/- 2.6 (8 patients); 3.4 +/- 3 (7 patients); and 4.5 +/- 5 (5 patients). Stage I is significantly different from Stages II and IV (P < 0.05). These preliminary results show an overall increasing trend in membrane-type 1 matrix metalloproteinase expression with increasing tumor stage. However, there was no correlation between membrane-type 1 matrix metalloproteinase expression and mucin production, degree of tumor differentiation, or vascular invasion.
Conclusion:
Preliminary results indicate that membrane-type 1 matrix metalloproteinase levels correlate with increasing tumor stage.
Insights
Membrane-type 1 matrix metalloproteinase mRNA expression increases with colorectal cancer stage. This suggests a role for membrane-type 1 matrix metalloproteinase in tumor progression, correlating with TNM staging.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Membrane-type matrix metalloproteinases (MT-MMPs) are proteolytic enzymes implicated in tumor invasion and metastasis.
- Membrane-type 1 matrix metalloproteinase (MT1-MMP) is the first identified member of this subclass.
- Understanding MT1-MMP expression is crucial for elucidating its role in cancer progression.
Purpose of the Study:
- To investigate the messenger RNA (mRNA) expression levels of membrane-type 1 matrix metalloproteinase (MT1-MMP) in colorectal cancer tissues.
- To determine the correlation between MT1-MMP mRNA expression and clinicopathological features of colorectal cancer, including TNM stage, tumor differentiation, mucin production, and vascular invasion.
Main Methods:
- Surgical specimens from colorectal adenocarcinoma patients were analyzed, comparing cancer and adjacent normal tissues.
- Northern blotting was employed to quantify MT1-MMP mRNA levels using a specific cDNA clone.
- Quantification was normalized against 18S rRNA, and results were expressed as the ratio of cancer to normal tissue expression. Statistical analysis used analysis of variance.
Main Results:
- A total of 32 samples were analyzed, revealing an increasing trend in MT1-MMP mRNA expression with advanced TNM stages (Stage I: 1.4, Stage II: 4.1, Stage III: 3.4, Stage IV: 4.5).
- Stage I expression was significantly lower than Stages II and IV (P < 0.05).
- No significant correlation was found between MT1-MMP expression and tumor differentiation, mucin production, or vascular invasion.
Conclusions:
- Preliminary findings indicate a positive correlation between MT1-MMP mRNA levels and increasing tumor stage in colorectal cancer.
- MT1-MMP may play a role in the progression of colorectal cancer, particularly in relation to TNM staging.