Inhibition of Ovarian Cancer Cell Spheroid Formation by Synthetic Peptides Derived from Nectin-4

• Published in: International journal of molecular sciences 2020-06, Vol.21 (13), p.4637
• Main Authors: Boylan, Kristin L M, Manion, Rory D, Shah, Heena, Skubitz, Keith M, Skubitz, Amy P N
• Format: Article
• Language: English
• Subjects: Aggregates; Ascites; Ascitic Fluid; Carcinoma, Ovarian Epithelial - drug therapy; Carcinoma, Ovarian Epithelial - metabolism; Cell adhesion; Cell adhesion & migration; Cell Adhesion - drug effects; Cell Adhesion - physiology; Cell adhesion molecules; Cell Adhesion Molecules - metabolism; Cell Adhesion Molecules - pharmacology; cell aggregation; Cell Aggregation - drug effects; Cell growth; Cell Line, Tumor; Cell Movement - drug effects; Chemotherapy; Cytotoxicity; Female; Humans; Medical prognosis; Medical research; Metastasis; Nectin; Nectin-4; Nectins - metabolism; Nectins - pharmacology; Ovarian cancer; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - metabolism; Ovary - metabolism; Peptides; Peptides - chemical synthesis; Peptides - pharmacology; Photography; Signal Transduction - drug effects; Spheroids; Spheroids, Cellular - drug effects; Synthetic peptides; Tumor cell lines; Tumor Cells, Cultured - drug effects
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21134637

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.