title: Lysophosphatidic Acid Stimulates Urokinase Receptor (uPAR/CD87) in Ovarian Epithelial Cancer Cells.
abstract: OBJECTIVE
  Lysophosphatidic acid (LPA) is a bioactive lipid positively linked with ovarian cancer progression. The multi-functional urokinase receptor (uPAR), a cell-surface glycoprotein, binds and facilitates activation of uPA and laterally regulates integrin and tyrosine kinase receptor activities in promotion of cell migration and invasion. We hypothesized that LPA stimulates uPAR expression and activity in ovarian epithelial cancer cells.
  
  
  METHODS
  Ovarian epithelial cancer cell lines OVCA 429 and OVCA 433 were stimulated with LPA and examined for uPAR mRNA expression and protein localization. uPA binding to OVCA plasma membranes was measured through enzymatic analysis of affinity-isolated cell-surface proteins.
  
  
  RESULTS
  LPA drove cell-surface uPAR aggregation and mRNA expression concomitant with increased cell-surface binding of uPA. Both control and LPA-stimulated uPAR expression and uPA cell-surface association involved phosphatidylinositol 3-kinase, but not p38 or p42 mitogen-activated protein kinase, signaling.
  
  
  CONCLUSIONS
  These data provide mechanistic insight into ovarian epithelial cancer cell progression by demonstrating that LPA drives uPAR expression and uPA binding.
authors.affiliation: Department of Biochemistry, Chemistry, and Engineering Sciences, Wartburg College, Waverly, IA, U.S.A.
authors.forename: Jason
authors.initials: J
authors.lastname: Lizalek
authors.affiliation: Department of Biochemistry, Chemistry, and Engineering Sciences, Wartburg College, Waverly, IA, U.S.A.
authors.forename: Tim
authors.initials: T
authors.lastname: McKenna
authors.affiliation: Department of Biochemistry, Chemistry, and Engineering Sciences, Wartburg College, Waverly, IA, U.S.A.
authors.forename: Kyle
authors.initials: K
authors.lastname: Huegel
authors.affiliation: Department of Biochemistry, Chemistry, and Engineering Sciences, Wartburg College, Waverly, IA, U.S.A.
authors.forename: Sydney
authors.initials: S
authors.lastname: Marsh
authors.affiliation: Department of Biochemistry, Chemistry, and Engineering Sciences, Wartburg College, Waverly, IA, U.S.A.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Carolan
authors.affiliation: Department of Biochemistry, Chemistry, and Engineering Sciences, Wartburg College, Waverly, IA, U.S.A.
authors.forename: Amy
authors.initials: A
authors.lastname: Kobliska
authors.affiliation: Department of Biochemistry, Chemistry, and Engineering Sciences, Wartburg College, Waverly, IA, U.S.A.
authors.forename: Emily
authors.initials: E
authors.lastname: Heying
authors.affiliation: Department of Biochemistry, Chemistry, and Engineering Sciences, Wartburg College, Waverly, IA, U.S.A.
authors.forename: Nicole
authors.initials: N
authors.lastname: Gardner
authors.affiliation: Department of Biochemistry, Chemistry, and Engineering Sciences, Wartburg College, Waverly, IA, U.S.A.
authors.forename: Geoff
authors.initials: G
authors.lastname: Miller
authors.affiliation: Department of Biochemistry, Chemistry, and Engineering Sciences, Wartburg College, Waverly, IA, U.S.A.
authors.forename: Aaron
authors.initials: A
authors.lastname: Kotecki
authors.affiliation: Department of Biochemistry, Chemistry, and Engineering Sciences, Wartburg College, Waverly, IA, U.S.A.
authors.forename: Meghan
authors.initials: M
authors.lastname: Henningsen
authors.affiliation: Department of Biochemistry, Chemistry, and Engineering Sciences, Wartburg College, Waverly, IA, U.S.A.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Lundt
authors.affiliation: Department of Biochemistry, Chemistry, and Engineering Sciences, Wartburg College, Waverly, IA, U.S.A.
authors.forename: Janean
authors.initials: J
authors.lastname: Farley
authors.affiliation: Department of Biochemistry, Chemistry, and Engineering Sciences, Wartburg College, Waverly, IA, U.S.A. shawn.ellerbroek@wartburg.edu.
authors.forename: Shawn M
authors.initials: SM
authors.lastname: Ellerbroek
mesh_terms: D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D008246:Lysophospholipids / Q000494:pharmacology*; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D055293:Receptors, Urokinase Plasminogen Activator / Q000235:genetics / Q000378:metabolism*; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
chemical_list: D008246:Lysophospholipids; C524898:PLAUR protein, human; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator; C032881:lysophosphatidic acid
keywords: Lysophosphatidic acid; PI3K; ovarian; uPA; uPAR