ABSTRACT
H ost cellular paracrine regulation of tumor progression is an important determinant of tumor growth, invasion and metastasis but one cell which has largely been ignored in this regulation is the myoepithelial cell. In any organ where there is significant branching morphogenesis such as the breast, myoepithelial cells ubiquitously accompany and surround epithelial cells and are thought to keep in check (negatively regulate) the process of branching. Myoepithelial cells surround both normal ducts and precancerous lesions, especially of the breast (so-called DCIS, ductal carcinoma-in-situ), and form a natural border separating proliferating epithelial cells from proliferating endothelial cells (angiogenesis). Myoepithelial cells, by forming this natural border, are thought to negatively regulate tumor invasion and metastasis. Whereas epithelial cells are susceptible targets for transforming events leading to cancer, myoepithelial cells are resistant. Indeed tumors of myoepithelial cells are uncommon and when they do occur, are almost always benign. Therefore it can be said that myoepithelial cells function as both autocrine as well as paracrine tumor suppressors. Our laboratory has found that myoepithelial cells secrete a number of suppressor molecules including high amounts of diverse proteinase inhibitors which include TIMP-1, protease nexin-II, and a-1 antitrypsin, but low amounts of proteinases and high amounts of diverse angiogenic inhibitors which include thrombospondin-1 and soluble bFGF receptors but low amounts of angiogenic factors compared to common malignant cell lines. However the most striking difference between the suppressive effector molecules secreted by myoepithelial cells and carcinoma cells is the levels of maspin secretion. Whereas carcinoma cells do not secrete maspin, myoepithelial cells secrete this serpin in large quantities. This observation holds in vitro, in mice, and in humans and suggests that maspin and myoepithelial cells exert pleiotropic suppressive effects on tumor progression. Since maspin is both a proteinase inhibitor, a locomotion inhibitor and an angiogenesis inhibitor, the diverse actions of maspin may largely explain the pronounced anti-invasive and anti-angiogenic effects of myoepithelial cells on carcinoma and pre-carcinoma cells. The same actions of maspin also may account for the low grade biology of myoepithelial tumors which are devoid of appreciable angiogenesis and invasive behavior. Finally since maspin is a secretory product of myoepithelial cells, the presence of maspin in body fluids such as in breast ductal fluid and in saliva reflects the structural and functional integrity of the
M aspin , edited by Mary J.C. Hendrix. ©2002 Eurekah.com
ductal-lobular units of the mammary and salivary glands respectively Maspin, in duc tal fluid, may serve as a surrogate (intermediate) end point marker (SEM) to estimate the risk of DCIS progression to invasive cancer in the breast and alternatively, in saliva, may serve as a tumor marker to detect the presence of incipient myoepithelial tumors occurring within the salivary glands of the head and neck.
