Ovarian Cancer Research Today is a free monthly online journal that collates and summarizes the latest research about Ovarian Cancer, including details on symptoms, causes, treatment, information.

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

Gil OD, Lee C, Ariztia EV, Wang FQ, Smith PJ, Hope JM, Fishman DA

Department of Obstetrics and Gynecology, New York University School of Medicine, 550 First Avenue, TH-528, New York, NY 10016, USA.

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.

Published 5 February 2008 in Gynecol Oncol, 108(2): 361-9.
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