341 Proteases in breast cancer

Abstract

Cancer invasion is dependent on a combined action of several proteolytic enzymes, such as collagenases, other metalloproteases, and serine proteases. Cathepsin-D was the first example of a protease whose immunoassay in the cytosol of breast tumors was available and could be readily standardized with quality control. Most studies indicated a worse prognosis in high Cathepsin-D tumors. Urokinase-type plasminogen activator (UPA), urokinase receptor (UPAR), and 2 plasminogen activator inhibitors, PAI1 and PAI-2, are all involved in regulation of plasmine generation. UPA and PAI1 levels in breast cancer tissue are independant and significant prognostic markers and high levels of each of the parameters are associated with poor prognostic. In tumors with high UPA or PAI1 content, a high level of PAI-2 appeared to be an independant marker of favorable prognostic. However, components of proteolytic enzyme systems are often expressed in non malignant stromal cells in invasive areas of cancer tissue. The cellular expression pattern of these molecules appears to be characteristic for each type of cancer and is not yet fully clarified. The measurements of proteases could be helpful for classifying breast tumors for understanding processes of breast tumor invasion and metastasis, and for the development of future treatment strategies based on interference in the proteolytic cascade which lead to tumor dissemination.