title: Lysophosphatidic acid (LPA) promotes E-cadherin ectodomain shedding and OVCA429 cell invasion in an uPA-dependent manner.
abstract: OBJECTIVE
  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.
authors: Department of Obstetrics and Gynecology, New York University School of Medicine, 550 First Avenue, TH-528, New York, NY 10016, USA.
authors: Orlando D
authors: OD
authors: Gil
authors: Catherine
authors: C
authors: Lee
authors: Edgardo V
authors: EV
authors: Ariztia
authors: Feng-Qiang
authors: FQ
authors: Wang
authors: Phillip J
authors: PJ
authors: Smith
authors: Joanie Mayer
authors: JM
authors: Hope
authors: David A
authors: DA
authors: Fishman
mesh_terms: D015820:Cadherins / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000235:genetics; D008246:Lysophospholipids / Q000494:pharmacology*; D009361:Neoplasm Invasiveness; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D015820:Cadherins; D007141:Immunoglobulin Fc Fragments; D008246:Lysophospholipids; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D014568:Urokinase-Type Plasminogen Activator; C032881:lysophosphatidic acid