This project had one Specific Aim after the peer and programmatic reviews, to evaluate prostasin, a glycosylphosphatidylinositol (GPI)-anchored extracellular serine protease as a potential metastasis suppressor of breast cancer in nude mice models. Two types of breast cancer metastasis, experimental and spontaneous, were to be used with the cell lines MDA-MB-231 and MDA-MB-435, respectively. We have found that prostasin must be activated by another membrane serine protease, matriptase before becoming functionally active as a proteolytic enzyme. The activating enzyme matriptase, however, is not expressed by either of the two model cell lines, an essential factor previously unrecognized, as well as an underlying reason for our previous inconsistent findings concerning prostasin s impact on breast cancer cell metastasis. In future research on membrane serine proteases in breast cancer cell biology, the newly recognized proteolytic cascade should be addressed with consideration of all of its current and potentially new member proteases.
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