The cell surface protease membrane-type serine protease-1 (MT-SP1), also known as matriptase, is often upregulated in epithelial cancers. We hypothesized that dysregulation of MT-SP1 with regard to its cognate inhibitor hepatocyte growth factor activator inhibitor-1 (HAI-1), a situation that increases proteolytic activity, might be exploited for imaging purposes to differentiate malignant from normal tissue. In this study, we show that MT-SP1 is active on cancer cells and that its activity may be targeted in vivo for tumor detection. A proteolytic activity assay with several MT-SP1-positive human cancer cell lines showed that MT-SP1 antibodies that inhibit recombinant enzyme activity in vitro also bind and inhibit the full-length enzyme expressed on cells. In contrast, in the same assay, MT-SP1-negative cancer cell lines were inactive. Fluorescence microscopy confirmed the cell surface localization of labeled antibodies bound to MT-SP1-positive cells. To evaluate in vivo targeting capability, 0.7 to 2 nmoles of fluorescently labeled antibodies were administered to mice bearing tumors that were positive or negative for MT-SP1. Antibodies localized to MT-SP1-positive tumors (n = 3), permitting visualization of MT-SP1 activity, whereas MT-SP1-negative tumors (n = 2) were not visualized. Our findings define MT-SP1 activity as a useful biomarker to visualize epithelial cancers using a noninvasive antibody-based method.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.
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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.