A unique aspect of ovarian cancer progression is the collection of ascites fluid in the abdominal cavity, which contains free-floating tumor cells in the form of single cells and also multicellular aggregates or spheroids. Spheroids are more resistant to standard chemotherapy due in part to their slow proliferation rate and also to the protection afforded by the tight cell aggregation. Agents that prevent spheroid formation have the potential to improve chemotherapeutic response. Our previous work on the function of the cell surface adhesion molecule Nectin-4 in ovarian cancer demonstrates that it plays a key role in the formation of ovarian cancer spheroids. We also showed that synthetic peptides derived from the amino acid sequences of Nectin-4 and its binding partner Nectin-1 could inhibit cell adhesion in an in vitro assay. The purpose of this study was to further examine the role of Nectin-4 in the formation of ovarian cancer spheroids using live-cell digital microscopy to monitor spheroid formation over time. Synthetic peptides derived from the amino acid sequences of Nectin-4 and Nectin-1 were tested for their ability to alter the spheroid formation of two ovarian cancer cell lines. Several peptides disrupted ovarian cancer spheroid formation, warranting further investigation. For the peptide with the strongest inhibitory effect on spheroid formation, we tested scrambled versions of the peptide, which did not affect the formation of spheroids. This peptide also inhibited spheroid formation in a concentration-dependent manner and was not cytotoxic. These results suggest that Nectin-derived peptides could augment the effect of chemotherapy, as they would maintain the cancer cells as single cells or small aggregates that are more sensitive to chemotherapy.

Citation Format: Kristin L.M. Boylan, Rory D. Manion, Heena Shah, Amy P.N. Skubitz. Synthetic peptides derived from the cell adhesion molecule Nectin-4 inhibit the formation of ovarian cancer 3D spheroids [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr A06.