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

Gynecol Oncol. 2008 Feb;108(2):361-9. doi: 10.1016/j.ygyno.2007.10.027.


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.

MeSH terms

  • Cadherins / biosynthesis*
  • Cadherins / genetics
  • Cell Line, Tumor
  • Down-Regulation
  • Female
  • Humans
  • Immunoglobulin Fc Fragments / genetics
  • Lysophospholipids / pharmacology*
  • Neoplasm Invasiveness
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology*
  • Protein Structure, Tertiary
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Recombinant Fusion Proteins / pharmacology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Urokinase-Type Plasminogen Activator / antagonists & inhibitors
  • Urokinase-Type Plasminogen Activator / metabolism*


  • Cadherins
  • Immunoglobulin Fc Fragments
  • Lysophospholipids
  • RNA, Messenger
  • Recombinant Fusion Proteins
  • Urokinase-Type Plasminogen Activator
  • lysophosphatidic acid