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

Overview

Journal J Oncol

Specialty Oncology

Date 2012 May 18

PMID 22593767

Citations 15

Authors

Yueying Liu

Rebecca Burkhalter

Jaime Symowicz

Kim Chaffin

Shawn Ellerbroek

M Sharon Stack

Affiliations

Soon will be listed here.

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.

Citing Articles

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Autotaxin/Lysophosphatidic Acid Axis: From Bone Biology to Bone Disorders.

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Malignant Ascites in Ovarian Cancer: Cellular, Acellular, and Biophysical Determinants of Molecular Characteristics and Therapy Response.

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Lysophosphatidic acid modulates ovarian cancer multicellular aggregate assembly and metastatic dissemination.

Klymenko Y, Bos B, Campbell L, Loughran E, Liu Y, Yang J Sci Rep. 2020; 10(1):10877.

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