The expression of Nectin-4 on the surface of ovarian cancer cells alters their ability to adhere, migrate, aggregate, and proliferate
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Kristin L.M. Boylan1, Petra C. Buchanan1, Rory D. Manion1, Dip M. Shukla1, Kelly Braumberger1, Cody Bruggemeyer1, Amy P.N. Skubitz1
1Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA
Amy P.N. Skubitz, email: [email protected]
Keywords: Nectin-4, ovarian cancer, cell adhesion, spheroids, migration
Received: February 11, 2016 Accepted: December 05, 2016 Published: December 25, 2016
The cell adhesion molecule Nectin-4 is overexpressed in epithelial cancers, including ovarian cancer. The objective of this study was to determine the biological significance of Nectin-4 in the adhesion, aggregation, migration, and proliferation of ovarian cancer cells. Nectin-4 and its binding partner Nectin-1 were detected in patients’ primary tumors, omental metastases, and ascites cells. The human cell lines NIH:OVCAR5 and CAOV3 were genetically modified to alter Nectin-4 expression. Cells that overexpressed Nectin-4 adhered to Nectin-1 in a concentration and time-dependent manner, and adhesion was inhibited by antibodies to Nectin-4 and Nectin-1, as well as synthetic Nectin peptides. In functional assays, CAOV3 cells with Nectin-4 knock-down were unable to form spheroids and migrated more slowly than CAOV3 parental cells expressing Nectin-4. NIH:OVCAR5 parental cells proliferated more rapidly, migrated faster, and formed larger spheroids than either the Nectin-4 knock-down or over-expressing cells. Parental cell lines expressed higher levels of epithelial markers and lower levels of mesenchymal markers compared to Nectin-4 knock-down cells, suggesting a role for Nectin-4 in epithelial-mesenchymal transition. Our results demonstrate that Nectin-4 promotes cell-cell adhesion, migration, and proliferation. Understanding the biology of Nectin-4 in ovarian cancer progression is critical to facilitate its development as a novel therapeutic target.
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