Paradoxical stimulation of matrix metalloproteinase-9 expression in HT1080 cells by a broad-spectrum hydroxamate-based matrix metalloproteinase inhibitor.

Due to their unusual ability to cleave and degrade a variety of ECM components, including triple-helical type IV collagen, two members of the family of matrix metalloproteinases (MMPs), MMP-2 and MMP-9, are thought to play critical roles during tumor invasion and metastasis. The proteolytic activity of mature MMPs is modulated by a group of specific inhibitors, the tissue inhibitors of metalloproteinases (TIMPs). Excessive ECM degradation observed during tumor invasion and metastasis frequently correlates with an excess of active MMPs. Therefore, adding exogenous inhibitors was contemplated for anticancer therapy. Indeed, synthetic MMP inhibitors have been demonstrated to reduce tumor invasion and metastasis in several in vitro and in vivo models.