Maspin and Cathepsin D Partnership in Regulating Mammary Gland Development and Breast Cancer, pp. 161-176
Authors: Zhila Khalkhali-Ellis, Ming Zhang, Mary J.C. Hendrix, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois and others
Abstract: Maspin (mammary serine protease inhibitor) was identified in 1994 by subtractive hybridization analysis of normal mammary tissue and breast cancer cell lines. Although Maspin exhibited sequence homology with members of the serine protease inhibitor superfamily, based on its structure and in the absence of an identified protease ligand, Maspin was considered a non-inhibitory serpin. Maspin is expressed in myoepithelial, epithelial and adipocyte components of mammary tissue, and plays a critical role in mammary gland development. After a decade of intensive research, Maspin is now recognized as a multifaceted protein, interacting with a diverse group of intra- and extra-cellular proteins, regulating a multitude of cellular functions. Our laboratory has identified the aspartyl lysosomal proteinase cathepsin D (CatD) as a putative Maspin binding partner. Apart from its well studied function in intercellular clearance of proteins, CatD is critically involved in apoptotic cell death. In addition, excessive production and aberrant secretion of CatD are believed to contribute to breast cancer progression and metastasis. To date, our studies have illuminated novel aspects of the CatD and Maspin partnership in regulating key stages of normal mammary gland differentiation and remodeling. In this short communication we will examine this complex interaction, and speculate on how alteration in pathways operative in mammary gland remodeling could promote malignant growth.