Proliferative effects of apical, but not basal, matrix metalloproteinase-7 activity in polarized MDCK cells.

Harrell PC, McCawley LJ, Fingleton B, McIntyre JO, Matrisian LM
Exp Cell Res. 2005 303 (2): 308-20

PMID: 15652345 · DOI:10.1016/j.yexcr.2004.09.020

Matrix metalloproteinase-7 (MMP-7) is primarily expressed in glandular epithelium. Therefore, its mechanism of action may be influenced by its regulated vectorial release to either the apical and/or basolateral compartments, where it would act on its various substrates. To gain a better understanding of where MMP-7 is released in polarized epithelium, we have analyzed its pattern of secretion in polarized MDCK cells expressing stably transfected human MMP-7 (MDCK-MMP-7), and HCA-7 and Caco2 human colon cancer cell lines. In all cell lines, latent MMP-7 was secreted to both cellular compartments, but was 1.5- to 3-fold more abundant in the basolateral compartment as compared to the apical. However, studies in the MDCK system demonstrated that MMP-7 activity was 2-fold greater in the apical compartment of MDCK-MMP-7(HIGH)-polarized monolayers, which suggests the apical co-release of an MMP-7 activator. In functional assays, MMP-7 over-expression increased cell saturation density as a result of increased cell proliferation with no effect on apoptosis. Apical MMP-7 activity was shown to be responsible for the proliferative effect, which occurred, as demonstrated by media transfer experiments, through cleavage of an apical substrate and not through the generation of a soluble factor. Taken together, our findings demonstrate the importance of MMP-7 secretion in relation to its mechanism of action when expressed in a polarized epithelium.

MeSH Terms (11)

Animals Caco-2 Cells Cell Line Cell Membrane Cell Polarity Cell Proliferation Dogs Humans Matrix Metalloproteinase 7 Metalloendopeptidases Transfection

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