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

Journal Article · Tue Feb 15 00:00:00 EST 2005 · Experimental Cell Research

DOI:https://doi.org/10.1016/j.yexcr.2004.09.020· OSTI ID:20717536

Harrell, Permila C ^[1]; McCawley, Lisa J ^[1]; Fingleton, Barbara ^[1]; McIntyre, J Oliver ^[1]; Matrisian, Lynn M ^[1]

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1. Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN 37232 (United States)

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{sup 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.

• OSTI ID: 20717536
• Journal Information: Experimental Cell Research, Vol. 303, Issue 2; Other Information: DOI: 10.1016/j.yexcr.2004.09.020; PII: S0014-4827(04)00574-9; Copyright (c) 2004 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0014-4827
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
APOPTOSIS
CATTLE
CELL PROLIFERATION
DEOXYURIDINE
DOGS
EPITHELIUM
GLYCOPROTEINS
GROWTH FACTORS
HEPARIN
KIDNEYS
LARGE INTESTINE
NEOPLASMS
PLASMINOGEN
RECEPTORS
SECRETION
SUBSTRATES
UROKINASE