lysophosphatidic acid disrupts junctional integrity and epithelial cohesion in ovarian cancer cells
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ID: 242818
2012
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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.
| Reference Key |
liu2012journallysophosphatidic
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|---|---|
| Authors | ;Yueying Liu;Rebecca Burkhalter;Jaime Symowicz;Kim Chaffin;Shawn Ellerbroek;M. Sharon Stack |
| Journal | joule |
| Year | 2012 |
| DOI |
10.1155/2012/501492
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| URL | |
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