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Membrane-type matrix metalloproteinases (MT-MMPs) in cell invasion
1Department of Molecular Virology and Oncology, Kanazawa University, Japan. vhsato@kenroku.ipc.kanazawa-u.ac.jp
Abstract:
Activated gelatinase A is reportedly associated with tumor spread. We identified a novel matrix metalloproteinase that localizes on the cell surface and mediate the activation of progelatinase A. Thus, this progelatinase A activator was named membrane-type matrix metalloproteinase (MT1-MMP). Following the first-discovery of MT1-MMP, two other MT-MMPs which can activate progelatinase A were identified (MT2- and MT3-MMP, respectively). Among these three MT-MMPs, MT1-MMP is most often overexpressed in malignant tumor tissues, including lung and stomach carcinomas that contain activated gelatinase A. This suggests that MT1-MMP is most closely associated with the activation of progelatinase A in these tumor tissues. The expression of MT1-MMP also induced binding of gelatinase A to the cell surface by functioning as a receptor. The cell surface localization of proteinases has advantages over pericellular proteolysis. MT1-MMP and its family may play a central role in the cell surface localization and activation of progelatinase A and via this mechanism, tumor cells use exogenous progelatinase A to mediate the proteolysis associated with invasion and metastasis.
Insights
Researchers discovered membrane-type matrix metalloproteinase (MT1-MMP), a cell-surface protein crucial for activating gelatinase A. This protein is linked to tumor spread and metastasis in various cancers.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Activated gelatinase A is implicated in tumor invasion and metastasis.
- Matrix metalloproteinases (MMPs) play a role in extracellular matrix degradation.
- Cell surface proteinases offer advantages for localized proteolysis.
Purpose of the Study:
- To identify novel activators of progelatinase A.
- To investigate the role of cell surface matrix metalloproteinases in gelatinase A activation.
- To explore the association of MT1-MMP with tumor progression.
Main Methods:
- Identification and characterization of a novel cell surface matrix metalloproteinase.
- Analysis of MT1-MMP expression in tumor tissues.
- Investigation of MT1-MMP's function in gelatinase A activation and cell surface binding.
Main Results:
- A novel membrane-type matrix metalloproteinase (MT1-MMP) was identified, mediating progelatinase A activation.
- MT1-MMP localizes to the cell surface and acts as a receptor for gelatinase A.
- MT1-MMP is overexpressed in malignant tumors (e.g., lung, stomach carcinomas) associated with activated gelatinase A.
- Two additional MT-MMPs (MT2- and MT3-MMP) were also identified as progelatinase A activators.
Conclusions:
- MT1-MMP and its family are key regulators of cell surface progelatinase A localization and activation.
- Tumor cells utilize MT1-MMP to activate exogenous progelatinase A for proteolysis, facilitating invasion and metastasis.
- MT1-MMP represents a significant factor in the proteolytic mechanisms driving tumor spread.