The myoepithelial defense: a host defense against cancer

Abstract

The behavior of human tumors depends not only on the nature of the tumor cells themselves but also on the modifying effects of various normal host cells such as fibroblasts and endothelial cells. One cell type, however — the myoepithelial cell — has not been studied scientifically. Myoepithelial cells normally surround ducts and acini of glandular organs such as the breast and salivary glands and contribute to the synthesis of a surrounding basement membrane. This relationship suggests that myoepithelial cells may exert paracrine effects on glandular epithelium and also regulate the progression of ductal carcinoma in situ (DCIS) to invasive carcinoma. Myoepithelial tumors, in turn, tend to be benign or low-grade neoplasms that exhibit the rare property of accumulating rather than degrading extracellular matrix material. To better understand the nature of myoepithelial tumors, as well as the possible role of normal myoepithelial host cells in cancer, we have established immortal cell lines and a number of transplantable xenografts from various human myoepithelial tumors of the salivary gland and breast. The cell lines exhibit a normal myoepithelial phenotype and the xenografts continue to accumulate an abundant extracellular matrix. Further ultrastructural, immunocytochemical, molecular, and bochemical studies reveal that myoepithelial cells secrete relatively low levels of matrix-degrading proteinases but relatively high levels of maspin and various other anti-invasive proteinase inhibitors, that some of these inhibitors accumulate within the myoepithelial matrix, and that myoepithelial cells can induce epithelial morphogenesis (spheroid formation) and inhibit tumor-cell invasion in vitro. Myoepithelial cells, which surround normal breast ducts and DCIS, have also been found to selectively express maspin and certain proteinase inhibitors in situ. These inherent myoepithelial properties are likely to contribute to the low-grade nature of myoepithelial neoplasms and advance our hypothesis that host myoepithelial cells regulate the progression of in situ to invasive carcinoma by providing an important host defense against cancer invasion.