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Metastasis of a primary tumor to a distant site is determined through signaling cascades that break down interactions between the cell and extracellular matrix proteins. Among the proteins mediating metastasis are serine proteases, such as neutrophil elastase. Serpins are family of serine protease inhibitors, contain a stretch of peptide that mimics a true substrate for a corresponding serine protease. Serine proteases bind to this substrate mimic in a 1:1 stoichiometric fashion and become catalytically inactive. Aberrant expression of serpin family members can contribute to a number of conditions, including emphysema (-1 antitrypsin deficiency), fatal bleeding (elastase to Thrombin specificity) and thrombosis (antithrombin deficiency), and are indicators of cancer stage phenotypes (circulating levels of squamous cell carcinoma antigen, known as SCCA1, increase in advancing stages of some cervical, lung, esophageal and head and neck cancers). SCCA1 expression has been demonstrated to promote oncogenic transformation and epithelial-mesenchymal transition (EMT) in mammary epithelial cells, and its silencing in breast cancer cells has been shown to halt their proliferation.
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