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Significance of membrane type 1 matrix metalloproteinase expression in breast cancer
1Department of Surgery, Tokyo Metropolitan Komagome Hospital.
Abstract:
Expression of matrix metalloproteinases (MMPs) plays an essential role in tumor metastasis and invasion through the degradation of extracellular matrix (ECM). MT1-MMP (membrane type 1 matrix metalloproteinase), a membrane-type MMP, is responsible for the activation of MMP2. In this study the significance of MT1-MMP expression in human breast tumors was investigated by immunocytochemical assay, and its correlation with clinicobiological features was analyzed. MT1-MMP expression was detected in tumor cells and/or stromal cells, and there was a strong correlation between the expressions of MT1-MMP in the two cell types. Out of 183 primary tumors, 103 (56.2%) showed positive staining of MT1-MMP in tumor cells. MT1-MMP expression showed no significant correlation with any of the clinicobiological parameters examined, including hormone receptor status and angiogenesis. In postoperative survival analysis, MT1-MMP expression itself was not a significant prognostic factor. However, in the particular subgroup with the accumulation of thymidine phosphorylase (TP)-positive stromal cells, which have been activated by various stimuli, such as cytokines and hypoxia, MT1-MMP expression had a significant prognostic value. These data suggested that MT1-MMP might function cooperatively with tumor-associated stromal cells for the progression of breast cancer.
Insights
Membrane type 1 matrix metalloproteinase (MT1-MMP) expression in breast tumors is common. While not a direct prognostic factor, MT1-MMP combined with thymidine phosphorylase-positive stromal cells indicates poorer outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Matrix metalloproteinases (MMPs) facilitate tumor metastasis by degrading the extracellular matrix (ECM).
- Membrane type 1 matrix metalloproteinase (MT1-MMP) is crucial for activating MMP2 and is implicated in cancer progression.
Purpose of the Study:
- To investigate the significance of MT1-MMP expression in human breast tumors.
- To analyze the correlation between MT1-MMP expression and clinicobiological features.
- To assess the prognostic value of MT1-MMP in breast cancer survival.
Main Methods:
- Immunocytochemical assay was used to detect MT1-MMP expression in 183 primary breast tumors.
- Correlation analysis was performed between MT1-MMP expression and clinicobiological parameters.
- Postoperative survival analysis was conducted to evaluate prognostic significance.
Main Results:
- MT1-MMP expression was observed in 56.2% of tumor cells and showed strong correlation between tumor and stromal cell expression.
- No significant correlation was found between MT1-MMP expression and clinicobiological parameters like hormone receptor status or angiogenesis.
- MT1-MMP alone was not a significant prognostic factor, but its expression was significant in patients with high thymidine phosphorylase (TP)-positive stromal cells.
Conclusions:
- MT1-MMP expression is prevalent in breast tumors and can be found in both tumor and stromal cells.
- MT1-MMP's prognostic value is context-dependent, becoming significant when co-expressed with TP-positive stromal cells.
- MT1-MMP may cooperate with tumor-associated stromal cells to drive breast cancer progression.