Matrix metalloproteinase in mammary gland remodeling-modulation by glycosaminoglycans

Mammary gland which undergoes proliferation, differentiation and involution in adult life is a useful model system to study the role of extracellular matrix (ECM) in regulating tissue specific functions. The involution that f ollows weaning results in the suppression of casein gene expression, collap se of alveolar structures and degradation of basement membrane as evidenced by biochemical analysis of matrix components like proteoglycans and collag en. Differential expression of three different MMPs viz. 130 K, 68 K and 60 K with varying specificity to Col IV of basement membrane and Col I of str oma, their selective inhibition by TIMP and proteoglycans and modulation by estrogen highlight the importance of these in the remodeling of the ECM in the mammary gland. The inhibition of these MMPs by glycosaminoglycans, par ticularly CS and change in the concentration of CS at different stages of m ammary gland development suggests the existence of a novel mechanism for th e regulation of the activity of MMPs at extracellular sites.