Campus Units

Chemical and Biological Engineering, Genetics, Development and Cell Biology, Molecular, Cellular and Developmental Biology

Document Type

Article

Research Focus Area

Health Care Technology and Biomedical Engineering

Publication Version

Accepted Manuscript

Publication Date

7-18-2014

Journal or Book Title

Biochemical and Biophysical Research Communications

Volume

450

Issue

1

First Page

213

Last Page

218

DOI

10.1016/j.bbrc.2014.05.086

Abstract

Matrix metalloproteinases (MMPs) are extracellular matrix (ECM) degrading enzymes and have complex and specific regulation networks. This includes activation interactions, where one MMP family member activates another. ECM degradation and MMP activation can be initiated by several different stimuli including changes in ECM mechanical properties or intracellular contractility. These mechanical stimuli are known enhancers of metastatic potential. MMP-14 facilitates local ECM degradation and is well known as a major mediator of cell migration, angiogenesis and invasion. Recently, function blocking antibodies have been developed to specifically block MMP-14, providing a useful tool for research as well as therapeutic applications. Here we utilize a selective MMP-14 function blocking antibody to delineate the role of MMP-14 as an activator of other MMPs in response to changes in cellular contractility and ECM stiffness. Inhibition using function blocking antibodies reveals that MMP-14 activates soluble MMPs like MMP-2 and -9 under various mechanical stimuli in the pancreatic cancer cell line, Panc-1. In addition, inhibition of MMP-14 abates Panc-1 cell extension into 3D gels to levels seen with non-specific pan-MMP inhibitors at higher concentrations. This strengthens the case for MMP function blocking antibodies as more potent and specific MMP inhibition therapeutics.

Comments

This is a manuscript of an article published as Haage, Amanda, Dong Hyun Nam, Xin Ge, and Ian C. Schneider. "Matrix metalloproteinase-14 is a mechanically regulated activator of secreted MMPs and invasion." Biochemical and biophysical research communications 450, no. 1 (2014): 213-218. DOI: 10.1016/j.bbrc.2014.05.086 . Copyright 2014 Elsevier Inc. Posted with permission.

Copyright Owner

Elsevier Inc.

Language

en

File Format

application/pdf

Published Version

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