Lysophosphatidic Acid Stimulates Urokinase Receptor (uPAR/CD87) in Ovarian Epithelial Cancer Cells. 2015

Jason Lizalek, and Tim McKenna, and Kyle Huegel, and Sydney Marsh, and Alexandra Carolan, and Amy Kobliska, and Emily Heying, and Nicole Gardner, and Geoff Miller, and Aaron Kotecki, and Meghan Henningsen, and Anastasia Lundt, and Janean Farley, and Shawn M Ellerbroek
Department of Biochemistry, Chemistry, and Engineering Sciences, Wartburg College, Waverly, IA, U.S.A.

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.

UI MeSH Term Description Entries
D008246 Lysophospholipids Derivatives of PHOSPHATIDIC ACIDS that lack one of its fatty acyl chains due to its hydrolytic removal. Lysophosphatidic Acids,Lysophospholipid,Acids, Lysophosphatidic
D009375 Neoplasms, Glandular and Epithelial Neoplasms composed of glandular tissue, an aggregation of epithelial cells that elaborate secretions, and of any type of epithelium itself. The concept does not refer to neoplasms located in the various glands or in epithelial tissue. Epithelial Cell Neoplasms,Glandular Cell Neoplasms,Epithelial Neoplasms,Glandular Neoplasms,Glandular and Epithelial Neoplasms,Neoplasms, Epithelial,Neoplasms, Glandular,Neoplasms, Glandular Epithelial,Cell Neoplasm, Epithelial,Cell Neoplasm, Glandular,Cell Neoplasms, Epithelial,Epithelial Cell Neoplasm,Epithelial Neoplasm,Epithelial Neoplasm, Glandular,Glandular Cell Neoplasm,Glandular Epithelial Neoplasm,Glandular Epithelial Neoplasms,Glandular Neoplasm,Neoplasm, Epithelial,Neoplasm, Epithelial Cell,Neoplasm, Glandular,Neoplasm, Glandular Cell,Neoplasm, Glandular Epithelial
D010051 Ovarian Neoplasms Tumors or cancer of the OVARY. These neoplasms can be benign or malignant. They are classified according to the tissue of origin, such as the surface EPITHELIUM, the stromal endocrine cells, and the totipotent GERM CELLS. Cancer of Ovary,Ovarian Cancer,Cancer of the Ovary,Neoplasms, Ovarian,Ovary Cancer,Ovary Neoplasms,Cancer, Ovarian,Cancer, Ovary,Cancers, Ovarian,Cancers, Ovary,Neoplasm, Ovarian,Neoplasm, Ovary,Neoplasms, Ovary,Ovarian Cancers,Ovarian Neoplasm,Ovary Cancers,Ovary Neoplasm
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000077216 Carcinoma, Ovarian Epithelial A malignant neoplasm that originates in cells on the surface EPITHELIUM of the ovary and is the most common form of ovarian cancer. There are five histologic subtypes: papillary serous, endometrioid, mucinous, clear cell, and transitional cell. Mutations in BRCA1, OPCML, PRKN, PIK3CA, AKT1, CTNNB1, RRAS2, and CDH1 genes are associated with this cancer. Epithelial Ovarian Cancer,Epithelial Ovarian Carcinoma,Ovarian Cancer, Epithelial,Ovarian Epithelial Cancer,Ovarian Epithelial Carcinoma,Cancer, Epithelial Ovarian,Cancer, Ovarian Epithelial,Carcinoma, Epithelial Ovarian,Epithelial Cancer, Ovarian,Epithelial Carcinoma, Ovarian,Epithelial Ovarian Cancers,Epithelial Ovarian Carcinomas,Ovarian Carcinoma, Epithelial,Ovarian Epithelial Cancers,Ovarian Epithelial Carcinomas
D014568 Urokinase-Type Plasminogen Activator A proteolytic enzyme that converts PLASMINOGEN to FIBRINOLYSIN where the preferential cleavage is between ARGININE and VALINE. It was isolated originally from human URINE, but is found in most tissues of most VERTEBRATES. Plasminogen Activator, Urokinase-Type,U-Plasminogen Activator,Urinary Plasminogen Activator,Urokinase,Abbokinase,Kidney Plasminogen Activator,Renokinase,Single-Chain Urokinase-Type Plasminogen Activator,U-PA,Single Chain Urokinase Type Plasminogen Activator,U Plasminogen Activator,Urokinase Type Plasminogen Activator
D045744 Cell Line, Tumor A cell line derived from cultured tumor cells. Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines
D055293 Receptors, Urokinase Plasminogen Activator An extracellular receptor specific for UROKINASE-TYPE PLASMINOGEN ACTIVATOR. It is attached to the cell membrane via a GLYCOSYLPHOSPHATIDYLINOSITOL LINKAGE and plays a role in the co-localization of urokinase-type plasminogen activator with PLASMINOGEN. Antigens, CD87,Urokinase Plasminogen Activator Receptor,Urokinase Type Plasminogen Activator Receptor,Urokinase-Type Plasminogen Activator Receptor,CD87 Antigen,Plasminogen Activator Receptor, Urokinase Type,Plasminogen Activator, Urokinase Receptor,Plasminogen Activator, Urokinase Receptors,Receptor, Pro-Urokinase,Receptor, Urokinase Plasminogen Activator,U-PA Receptor,Upar Receptor,Urokinase Plasminogen Activator Receptors,Urokinase-Type Plasminogen Activator Receptors,Antigen, CD87,CD87 Antigens,Pro-Urokinase Receptor,Receptor, Pro Urokinase,Receptor, U-PA,Receptor, Upar,U PA Receptor,Urokinase Type Plasminogen Activator Receptors

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