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dc.contributor.authorLiu, Yueyingeng
dc.contributor.corporatenameUniversity of Missouri--Columbia. School of Medicineeng
dc.date.issued2010-02eng
dc.description.abstractApproximately 22,000 U.S. women are newly diagnosed each year with epithelial ovarian cancer (EOC), 75% of whom present with existing metastases and peritoneal ascites. A key event in EOC metastasis is disruption of cell-cell contacts via modulation of intercellular junctional components such as cadherins. In contrast to most carcinomas, EOC actually gain expression of the cell-cell adhesion molecule Ecadherin. Ovarian cancer metastasizes via exfoliation of cells from the primary tumor to the peritoneal cavity, wherein free-floating cells and multi-cellular aggregates attach and invade to anchor growth of secondary lesions. Ascites is also rich in lysophosphatidic acid (LPA), a bioactive lipid that is a sensitive biomarker for ovarian cancer and may promote early events in ovarian cancer dissemination. The objective of this study was to determine whether LPA modulates E-cadherin junctional integrity. Immunofluorescence analyses were used to demonstrate a loss of junctional E-cadherin in OvCar3, OvCa429 and OvCa433cells exposed to LPA. LPA-induced loss of E-cadherin was concentration-and time-dependent. Surface labeling and western blotting showed that LPA promoted E-cadherin ectodomain shedding. Matrix metalloproteinase-9 (MMP9) expression was also induced by LPA treatment and inhibition of MMP9 activity blocked E-cadherin ectodomain shedding. Blocking LPA receptor signaling using the compound LPAR1 inhibited MMP9 expression and restored junctional E-cadherin staining. These data support a model wherein LPA induces MMP9 expression and MMP9-catalyzed E-cadherin ectodomain shedding, resulting in a loss of E-cadherin junctional integrity, facilitating metastatic dissemination of ovarian cancer cells.eng
dc.identifier.urihttp://hdl.handle.net/10355/6216
dc.languageEnglisheng
dc.relation.ispartofcommunityUniversity of Missouri--Columbia. Health Sciences Research Day.eng
dc.rightsOpenAccess.eng
dc.rights.licenseThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License.eng
dc.subjectepithelial ovarian cancereng
dc.subjectcadherinseng
dc.subject.FASTCadherinseng
dc.subject.FASTOvaries -- Cancereng
dc.subject.FASTOvaries -- Tumorseng
dc.titleDisruption of e-cadherin junctional integrity in ovarian cancer cells is promoted by LPA-induced MMP-9 activity [abstract]eng
dc.typeAbstracteng


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