dc.contributor.author | Liu, Yueying | eng |
dc.contributor.corporatename | University of Missouri--Columbia. School of Medicine | eng |
dc.contributor.meetingname | Health Sciences Research Day (2010 : University of Missouri) | eng |
dc.date.issued | 2010-02 | eng |
dc.description.abstract | Approximately 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.format.extent | 1 page | eng |
dc.identifier.uri | http://hdl.handle.net/10355/6216 | |
dc.language | English | eng |
dc.relation.ispartofcommunity | University of Missouri--Columbia. Health Sciences Research Day | eng |
dc.rights | OpenAccess. | eng |
dc.rights.license | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License. | eng |
dc.subject | epithelial ovarian cancer | eng |
dc.subject | cadherins | eng |
dc.subject.FAST | Cadherins | eng |
dc.subject.FAST | Ovaries -- Cancer | eng |
dc.subject.FAST | Ovaries -- Tumors | eng |
dc.title | Disruption of e-cadherin junctional integrity in ovarian cancer cells is promoted by LPA-induced MMP-9 activity [abstract] | eng |
dc.type | Abstract | eng |