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- Title
Lysophosphatidic Acid Disrupts Junctional Integrity and Epithelial Cohesion in Ovarian Cancer Cells.
- Authors
Yueying Liu; Burkhalter, Rebecca; Symowicz, Jaime; Chaffin, Kim; Ellerbroek, Shawn; Sharon Stack, M.
- 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 Ecadherin 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.
- Subjects
LYSOPHOSPHOLIPIDS; EPITHELIAL cells; OVARIAN cancer; CANCER cells; CADHERINS; CELL communication; JUNCTIONAL complexes (Epithelium); PROGNOSIS
- Publication
Journal of Oncology, 2012, p1
- ISSN
1687-8450
- Publication type
Article
- DOI
10.1155/2012/501492