Lysophosphatidic acid (LPA) promotes E-cadherin ectodomain shedding and OVCA429 cell invasion in an uPA-dependent manner. Academic Article uri icon

Overview

abstract

  • OBJECTIVES: To evaluate the role of LPA in regulating E-cadherin cell surface expression, adhesion, and invasion in epithelial ovarian carcinoma (EOC) cells. METHODS: E-cadherin mRNA expression in OVCA429 and IOSE-29 cells was evaluated by real-time RT-PCR. Immunofluorescence and Western blot analysis were performed to determine cell surface expression and shedding of E-cadherin 80-kDa soluble fragment by LPA. Kinetics of LPA-induced uPA activity was followed with a colorimetric enzymatic assay. Invasion assays were performed in a modified Boyden chamber where cells were allowed to migrate to the bottom compartment through a porous filter coated with collagen. Additionally we measured the 80-kDa form from the ascites of women with stage III/IV EOC. RESULTS: LPA induces E-cadherin shedding of a soluble 80-kDa fragment. We found that this process is mediated by the uPA proteolytic cascade. High levels of soluble E-cadherin were found in the ascites from women with advanced stage EOC. LPA and a soluble recombinant E-cadherin-Fc chimera promotes invasion of OVCA429 cells. CONCLUSIONS: LPA induces shedding of an 80-kDa E-cadherin-soluble fragment in an uPA-dependent manner and promotes in vitro invasion. High levels of soluble E-cadherin in malignant ascites may also affect ovarian metastasis.

publication date

  • February 1, 2008

Research

keywords

  • Cadherins
  • Lysophospholipids
  • Ovarian Neoplasms
  • Urokinase-Type Plasminogen Activator

Identity

Scopus Document Identifier

  • 38649131972

Digital Object Identifier (DOI)

  • 10.1016/j.ygyno.2007.10.027

PubMed ID

  • 18073130

Additional Document Info

volume

  • 108

issue

  • 2