The expression of Nectin-4 on the surface of ovarian cancer cells alters their ability to adhere, migrate, aggregate, and proliferate

Kristin L.M. Boylan, Petra C. Buchanan, Rory D. Manion, Dip M. Shukla, Kelly Braumberger, Cody Bruggemeyer, Amy P.N. Skubitz

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)9717-9738
Number of pages22
JournalOncotarget
Volume8
Issue number6
DOIs
StatePublished - Jan 1 2017

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Ovarian Neoplasms
nectins
Cell Line
Epithelial-Mesenchymal Transition
Cell Adhesion Molecules
Ascites
Cell Adhesion
Cell Movement
Neoplasms

Keywords

  • Cell adhesion
  • Migration
  • Nectin-4
  • Ovarian cancer
  • Spheroids

Cite this

The expression of Nectin-4 on the surface of ovarian cancer cells alters their ability to adhere, migrate, aggregate, and proliferate. / Boylan, Kristin L.M.; Buchanan, Petra C.; Manion, Rory D.; Shukla, Dip M.; Braumberger, Kelly; Bruggemeyer, Cody; Skubitz, Amy P.N.

In: Oncotarget, Vol. 8, No. 6, 01.01.2017, p. 9717-9738.

Research output: Contribution to journalArticle

Boylan, Kristin L.M. ; Buchanan, Petra C. ; Manion, Rory D. ; Shukla, Dip M. ; Braumberger, Kelly ; Bruggemeyer, Cody ; Skubitz, Amy P.N. / The expression of Nectin-4 on the surface of ovarian cancer cells alters their ability to adhere, migrate, aggregate, and proliferate. In: Oncotarget. 2017 ; Vol. 8, No. 6. pp. 9717-9738.
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