Cancer Associated Extracellular Enzymes

Expression and secretion of proteases by the tumor microenvironment is critical both for support of tumor progression and metastasis, activation of growth factors and promotion of angiogenesis and invasion by digestion of the extracellular matrix (matrix metalloproteinases, MMPs, are collagenases) [114], The dominant cancer proteases are cathepsins and MMPs with both extracellular secreted MMPs and membrane type MMPs (MT-MMPs). This has promoted the use of cathepsin and MMP substrate peptides for tumor imaging and/or therapy [ 115,116]. 

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Handbook of Polymers for Pharmaceutical Technologies 11.2.4 Cancer Associated Extracellular Enzymes... 

Matrix metalloproteinases (MMPs) are a class of zinc- and calcium-dependent enzymes that are responsible for the metabolism of extracellular matrix proteins [27]. Increased activity of MMPs has been associated with pathological diseases such as arthritis, cancer, multiple sclerosis and Alzheimer s disease [28-31]. Therefore, they constitute an important group of drug targets. Their inhibition is accomplished by blocking the active site of the catalytic domain with ligands that contain hydroxamic or carboxylic acids to chelate the Zn metal. The identification of low molecular weight compounds that contain different scaffolds may lead to the development of a new class of specific inhibitors. 

Several mechanisms can be proposed by which kallikreins can be involved in the pathogenesis of endocrine-related malignancies. Proteolytic enzymes are thought to be involved in tumor progression because of their role in extracellular matrix degradation. Many studies have shown that a variety of proteolytic enzymes are overproduced either by the cancer cells themselves or by the surrounding stromal cells, and that their overexpression is associated with unfavorable clinical prognosis [249],... 

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