Matriptase and HAI-1 are expressed by normal and malignant epithelial cells in vitro and in vivo

Matriptase and its cognate, Kunitz-type serine protease inhibitor, HAI-1, c omprise a newly characterized extracellular matrix-degrading protease syste m that may function as an epithelial membrane activator for other proteases and latent growth factors. both enzyme and inhibitor have been detected in breast cancer cells, immortalized mammary epithelial cells, and human milk , but not in cultured fibroblasts nor in fibrosarcoma cells. To test the hy pothesis that this system is expressed by normal breast epithelium, Invasiv e breast cancers, and other cancers of an epithelial origin (carcinomas) bu t not in cancers of a mesenchymal origin, we have expanded our expression a nalysis of matriptase and HAI-1 in vitro and in vivo. Matriptase and HAI-1 were detected at the protein and mRNA levels both in hormone-dependent and hormone-independent cultured breast cancer cells, and this expression corre lated with the expression of the epithelial markers E-cadherin or ZO-1. How ever, none of the breast cancer cell lines tested that express the mesenchy mal marker vimentin express matriptase or HAI-1, consistent with an epithel ial-selective expression of this system. Expression of matriptase, as deter mined by Western blot analysis, was observed in primary human breast, gynec ological, and colon carcinomas, but not in stromal-derived ovarian tumors a nd human sarcomas of various origins and histological grades. The epithelia l-selective expression of matriptase and HAI-1 was further confirmed in hum an breast cancers by immunohistochemistry and In situ hybridization, where the expression of the protease and the inhibitor were found in the carcinom a cells and in surrounding normal breast epithelia. The expression of the m atriptase/HAI-1 system by malignant epithelial cells in vivo suggests a pos sible role for this protease in multiple aspects of the pathophysiology of epithelial malignancy, including invasion and metastasis.