Chapter category: Cancer Metastasis
Maspin and Myoepithelial Cells
Maspin
Edited by: Mary J.C. HendrixISBN: 1-58706-097-3
» Get more information about this book at landesbioscience.com «
Chapter authors:
Sanford H. Barsky, Paul Kedeshian and Mary L. Alpaugh
Host 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 ductal-lobular units of the mammary and salivary glands respectively. Maspin, in ductal 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.
Additional chapters from this book:
Maspin, a Potential Prognostic Marker for Human Cancers
Mickey C-T. Hu, Weiya Xia and Mien-Chie Hung
Maspin (mammary serine protease inhibitor) is a 42 kDa protein that shares significant sequence homology with several members of the serpin (serine prot...
The Role of Maspin in Human Placental Development
Anuja Dokras, Lynn M.G. Gardner, Dawn A. Kirschmann, Elisabeth A. Seftor and Mary J.C. Hendrix
The human placenta is hemochorial and displays highly regulated invasive activity and exponential growth potential. The stem cell cytotrophoblasts undergo differentiation along two...
The Role of Maspin in Tumor Progression and Normal Development
Ming Zhang
Serine protease inhibitors (serpins) are comprised of a large family of molecules that play a variety of physiological roles in vivo.1-3 Not all molecules that in...
Maspin Suppresses Breast Cancer Cell Invasiveness by Modulating Integrin Expression and Function
Richard E.B. Seftor, Valerie A. Odero, Elisabeth A. Seftor and Mary J.C. Hendrix
Although the novel tumor suppressor gene maspin (mammary serine protease inhibitor) was originally isolated from normal mammary epithelium by subtractive hybridization and d...
Genetic and Epigenetic Regulation of Maspin Gene Expression in Normal and Tumor Tissue
Frederick E. Domann and Bernard W. Futscher
Maspin, a tumor suppressor gene, encodes a protein that has been shown to restrict breast cancer cell motility, invasion, and metastasis. Expression of the maspin gene is commonly ...
Maspin and Pericellular Plasminogen Activation in Cell-Matrix Interaction
Shijie Sheng, Hector Biliran Jr. and Richard McGowen
Maspin may offer a unique opportunity to block tumor invasion and metastasis. Maspin expression correlates with normality, and pre-malignant and/or less invasive lesions in breast,...
Maspin and Myoepithelial Cells
Sanford H. Barsky, Paul Kedeshian and Mary L. Alpaugh
Host 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 reg...
Maspin: Functional Insights from a Structural Perspective
Philip A. Pemberton
Since the seminal paper by Zou et al1 identifying the existence of the novel tumor suppressor maspin (mammary serpin), research efforts have largely focused on the mecha...
Maspin in the Sager Laboratory
Ming Zhang, Shijie Sheng and Arthur B. Pardee
Discovery of a disease-related gene marks only the beginning to a series of difficult investigations. In order to establish the functional role of the newly discovered gene, one...
Ruth Sager, Geneticist
Arthur B. Pardee
Ruth Sager named her favorite gene Maspin, mammary serpin protease inhibitor. Expression of this gene is lost in advanced breast cancers and inhibits tumor invasion and metastas...
