Matrix Metalloproteinases and Cancer Cell Invasion/Metastasis
A wealth of knowledge has accumulated over the past four decades on the importance of matrix metalloproteinases (MMPs) in cancer induction, invasion, and metastasis. This chapter aims to provide the reader with recent information to help understand the disconnect between experimental observations implicating the crucial role of MMPs in cancer progression and the historic failure of several broad-spectrum MMP inhibitors in clinical drug trials in advanced cancer. The chemistry and biology of the large MMP family and tissue inhibitors of MMPs (TIMPs) will be summarized. Complexity of MMP function in cancer will be described with an emphasis on pericellular cleavage of extracellular matrix (ECM) and non-ECM substrates. Production of MMPs by stromal cells within a tumor, as well as cancer cells, is well established. Anticancer effects of selected in MMPs are described. The study of cell migration within a three-dimensional collagen matrix has been responsible for broadening our understanding of cancer progression. The involvement of MMPs in the transition from noninvasive to invasive, metastatic cancer, and an emphasis on epithelial-to-mesenchymal transition (EMT) will be presented. New approaches to improve the specificity of MMP inhibitors for use in future clinical trials are discussed.
KeywordsCancer Cell Invasion Secrete Leukocyte Protease Inhibitor Circulate Cancer Cell Premetastatic Niche Extracellular Matrix Metalloproteinase Inducer
This work support was provided by a Merit Review Grant from the Department of Veterans Affairs, NIH grant (RO1 CA11355301A1), a Baldwin Breast Cancer Foundation grant and a Walk-for-Beauty grant from the Research Foundation, Stony Brook University.
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