Matrix Metalloproteinase-9 and Cell Division in Neuroblastoma Cells and Bone Marrow Macrophages

Matrix metalloproteinases (MMPs) degrade the extra cellular matrix and carry out key functions m cell development cancer injury and regeneration In addition to its well recognized extracellular action functional intracellular MMP activity under certain conditions is supported by increasing evidence In this study we observed higher gelatinase activity by in situ zymography and increased MMP 9 immunoreactivity in human neuroblastoma cells and m bone marrow macrophages undergoing mitosis compared with resting cells We studied the pattern of immuno reactivity at the different stages of cell division by confocal microscopy Immunostaining with different monoclonal antibodies against MMP 9 revealed a precise dynamic and well orchestrated localization of MMP 9 at the different stages of cell division The cellular distribution of MMP 9 staining was studied in relation to that of microtubules The spatial pattern of MMP 9 immunoreactivity suggested some participation in both the reorganization of the nuclear content and the process of chromatid segmentation We then used several MMP 9 inhibitors to find out whether MMP 9 might be involved in the cell cycle These drugs impaired the entry of cells into mitosis as revealed by flow cytometry and reduced cell culture growth In addition the silencing of MMP 9 expression with small interfering RNA also reduced cell growth Taken together these results suggest that intracellular MMP 9 is involved in the process of cell division in neuroblastoma cells and in primary cultures of macrophages (Am J Pathol 2010 177 2870-2885 DOI 10 2353/ajpath 2010 090050)