MMP-19: Cellular Localization of a Novel Metalloproteinase Within Normal Breast Tissue and Mammary Gland Tumours

Matrix metalloproteinases (MMPs) are instrumental in promoting and facilitating the spread of malignant diseases and in the de novo formation of blood vessels. This study has mapped the immunoreactivity of a novel, angiogenesis-related metalloproteinase--MMP-19--in normal breast tissue and in benign and malignant breast lesions and compared this pattern of expression with that of MMP-2. In the normal resting mammary gland, MMP-19 was strongly expressed in the myoepithelial layer of the ductal system; the alveolar and ductal epithelia displayed considerable, but lobule-specific, variations in labelling intensity. MMP-19 was also present within the smooth muscle and endothelial layers of large and medium-sized blood vessels, as well as within capillary walls. In benign lesions, all tumour cells and their surrounding vasculature were uniformly and strongly immunoreactive for MMP-19. Progression towards an invasive phenotype and neoplastic dedifferentiation led to the disappearance of MMP-19 from tumour cells and blood vessels and a concomitant rise in the levels of MMP-2. In vitro experiments conducted with isolated smooth muscle cells cultivated on a solid substratum, or within the interstices of a collagen matrix, indicated that the expression of MMP-19 is influenced by the architecture of the surrounding extracellular matrix.