Breast Cancer Metastasis and the Balance of the Serine Protease Matriptase and Its Inhibition KSPI-1

摘要

This study set out to evaluate the biological consequences of a shift in the ratio of the serine protease matriptase relative to its cognate inhibitor HAI-1. The goal of this work is to generate data that we believe will assist in evaluating whether the matriptase HAI-l system plays a role in breast cancer invasion and metastasis. In order to alter protease / inhibitor ratios we proposed to use a tetracycline regulable expression system to either increase matriptase levels by overexpression or reduce HAI-1 levels by expression of a ribozyme targeted to the HAI-1 mRNA. We have shown that at least in MCF-7 cells, increased expression of Matriptase does not have any impact on any of the properties of the cells that we have examined. This leads us to conclude that these cells either make enough Matriptase already, and additional enzyme is irrelevant, that sufficient HAI-1 is made by the cells to inhibit the activity of the extra Matriptase, or that Matriptase is irrelevant to these processes in these cells. Ongoing studies should allow us to distinguish between these possibilities.