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

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

Research output: Contribution to journalArticle

7 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; Buchanan, Petra C.; Manion, Rory D.; Shukla, Dip M.; Braumberger, Kelly; Bruggemeyer, Cody; Skubitz, Amy P.

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

Research output: Contribution to journalArticle

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