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Journal of Oncology
Volume 2012, Article ID 501492, 8 pages
http://dx.doi.org/10.1155/2012/501492
Research Article

Lysophosphatidic Acid Disrupts Junctional Integrity and Epithelial Cohesion in Ovarian Cancer Cells

1Department of Chemistry and Biochemistry, University of Notre Dame, 1234 Notre Dame Avenue, A200D Harper Hall, Notre Dame, IN 46557, USA
2Harper Cancer Research Institute, University of Notre Dame, 1234 Notre Dame Avenue, A200D Harper Hall, Notre Dame, IN 46557, USA
3Department of Medical Pharmacology and Physiology, University of Missouri School of Medicine, Columbia, MO 65212, USA
4Department of Cell and Molecular Biology, Northwestern University, Chicago, IL 60611, USA
5Department of Chemistry, Wartburg College, Waverly, IA 50677, USA

Received 14 December 2011; Accepted 6 February 2012

Academic Editor: Peter E. Schwartz

Copyright © 2012 Yueying Liu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Ovarian cancer metastasizes via exfoliation of free-floating cells and multicellular aggregates from the primary tumor to the peritoneal cavity. A key event in EOC metastasis is disruption of cell-cell contacts via modulation of intercellular junctional components including cadherins. Ascites is rich in lysophosphatidic acid (LPA), a bioactive lipid that may promote early events in ovarian cancer dissemination. The objective of this paper was to assess the effect of LPA on E-cadherin junctional integrity. We report a loss of junctional E-cadherin in OVCAR3, OVCA429, and OVCA433 cells exposed to LPA. LPA-induced loss of E-cadherin was concentration and time dependent. LPA increased MMP-9 expression and promoted MMP-9-catalyzed E-cadherin ectodomain shedding. Blocking LPA receptor signaling inhibited MMP-9 expression and restored junctional E-cadherin staining. LPA-treated cells demonstrated a significant decrease in epithelial cohesion. Together these data support a model wherein LPA induces MMP-9 expression and MMP-9-catalyzed E-cadherin ectodomain shedding, resulting in loss of E-cadherin junctional integrity and epithelial cohesion, facilitating metastatic dissemination of ovarian cancer cells.