Inhibiting effects of common trivalent metal ions on transmembrane-type 2 matrix metalloproteinase

Transmembrane-type 2 matrix metalloproteinase (MT2-MMP) degrades connective extracellular matrix between cells and enables tumor cells to migrate and metastasize, making this substance a potential therapeutic target in various diseases. In this work, the interactions between MT2-MMP and common trivalent metal ions, including aluminum (Al3+) and ferrum (Fe3+) ions, were investigated. Enzymatic detection revealed that Al3+ and Fe3+ strongly inhibited the MT2-MMP. Fluorescence spectrography elucidated a static quenching interaction between the negatively charged amino acids on MT2-MMP and the inhibitory trivalent metal ions, indicating that a stable complex was formed between MT2-MMP and metal ions. In addition, fluorescence data and molecular modeling analysis of the binding characteristics revealed that one trivalent metal ion bound with a protein in the stable complex formation process. The potential inhibitory effect of Al3+ on MT2-MMP was further examined in an MT2-MMP-overexpressed cell line, HT1080, by using flow cytometry. As a result, Al3+ can promote HT1080 cell apoptosis in a micromolar concentration-dependent manner. This work illustrated that common trivalent metal ions can potentially inhibit MT2-MMP-related tumors.