Inhibition of ovarian cancer cell spheroid formation by synthetic peptides derived from nectin-4

Kristin L.M. Boylan, Rory D. Manion, Heena Shah, Keith M Skubitz, Amy P Skubitz

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


The formation of 3D multicellular spheroids in the ascites fluid of ovarian cancer patients is an understudied component of the disease progression. Spheroids are less sensitive to chemotherapy, in part due to the protection afforded by their structure, but also due to their slower proliferation rate. Previous studies suggest that the cell adhesion molecule Nectin-4 plays a key role in the formation of ovarian cancer spheroids. In this study, we further examined the role of Nectin-4 at early time points in spheroid formation using real-time digital photography. Human NIH:OVCAR5 ovarian cancer cells formed aggregates within 8 h, which further contracted into compact spheroids over 24 h. In contrast, Nectin-4 knockdown cells did not form tightly compacted spheroids. Synthetic peptides derived from Nectin-4 were tested for their ability to alter spheroid formation in two ovarian cancer cell lines. Nectin-4 peptide 10 (N4-P10) had an immediate effect on disrupting ovarian cancer spheroid formation, which continued for over 24 h, while a scrambled version of the peptide had no effect. N4-P10 inhibited spheroid formation in a concentration-dependent manner and was not cytotoxic; suggesting that N4-P10 treatment could maintain the cancer cells as single cells which may be more sensitive to chemotherapy.

Original languageEnglish (US)
Article number4637
Pages (from-to)1-16
Number of pages16
JournalInternational journal of molecular sciences
Issue number13
StatePublished - Jul 1 2020

Bibliographical note

Funding Information:
Funding: This research was funded by the Minnesota Ovarian Cancer Alliance.

Funding Information:
This research was funded by the Minnesota Ovarian Cancer Alliance. Acknowledgments: We would like to acknowledge the technical advice and expertise of Martin Felices, Peter Howard, and Jeffrey S. Miller in the Department of Medicine at the University of Minnesota for the use of their IncuCyte? Zoom instrument, and Mark Sanders and Guillermo Marques at the University Imaging Centers (UIC) for the use of the IncyCyte? S3 instrument, and Thomas Pengo of the UIC for advice on image analysis software. We would like to thank Martina Bazzaro in the Department of Obstetrics, Gynecology and Women?s Health for the use of her Nikon TE200 microscope.

Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.


  • Ascites
  • Cell adhesion
  • Cell aggregation
  • Nectin-4
  • Ovarian cancer
  • Peptides
  • Spheroids

PubMed: MeSH publication types

  • Journal Article


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