Maspin and cathepsin d partnership in regulating mammary gland development and breast cancer

Maspin (mammary serine protease inhibitor) was identified in 1994by subtractive hybridization analysis of normal mammary tissue andbreast cancer cell lines. Although Maspin exhibited sequence homologywith members of the serine protease inhibitor superfamily, based on itsstructure and in the absence of an identified protease ligand, Maspin wasconsidered a non-inhibitory serpin. Maspin is expressed in myoepithelial,epithelial and adipocyte components of mammary tissue, and plays acritical role in mammary gland development. After a decade of intensiveresearch, Maspin is now recognized as a multifaceted protein, interactingwith a diverse group of intra- and extra-cellular proteins, regulating amultitude of cellular functions.Our laboratory has identified the aspartyl lysosomal proteinasecathepsin D (CatD) as a putative Maspin binding partner. Apart from itswell studied function in intercellular clearance of proteins, CatD iscritically involved in apoptotic cell death. In addition, excessiveproduction and aberrant secretion of CatD are believed to contribute tobreast cancer progression and metastasis. To date, our studies haveilluminated novel aspects of the CatD and Maspin partnership inregulating key stages of normal mammary gland differentiation andremodeling. In this short communication we will examine this complexinteraction, and speculate on how alteration in pathways operative inmammary gland remodeling could promote malignant growth.