title: The expression of Nectin-4 on the surface of ovarian cancer cells alters their ability to adhere, migrate, aggregate, and proliferate.
abstract: 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.
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Kristin L M
authors.initials: KL
authors.lastname: Boylan
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Petra C
authors.initials: PC
authors.lastname: Buchanan
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Rory D
authors.initials: RD
authors.lastname: Manion
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Dip M
authors.initials: DM
authors.lastname: Shukla
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Kelly
authors.initials: K
authors.lastname: Braumberger
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Cody
authors.initials: C
authors.lastname: Bruggemeyer
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Amy P N
authors.initials: AP
authors.lastname: Skubitz
mesh_terms: D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002449:Cell Aggregation; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000075983:Nectins / Q000378:metabolism; D009361:Neoplasm Invasiveness; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011485:Protein Binding; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection
chemical_list: D015815:Cell Adhesion Molecules; C000619010:NECTIN1 protein, human; D000075983:Nectins; C442228:NECTIN4 protein, human
keywords: Nectin-4; cell adhesion; migration; ovarian cancer; spheroids