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

Autor:	Keith M. Skubitz, Kristin L.M. Boylan, Rory D. Manion, Amy P.N. Skubitz, Heena Shah
Rok vydání:	2020
Předmět:	Nectins Cell spheroids Carcinoma Ovarian Epithelial Article Catalysis lcsh:Chemistry Inorganic Chemistry ascites Cell Movement Cell Line Tumor Spheroids Cellular Tumor Cells Cultured medicine Ascitic Fluid Humans Cytotoxic T cell Physical and Theoretical Chemistry Cell adhesion lcsh:QH301-705.5 Molecular Biology Spectroscopy Ovarian Neoplasms Chemistry Cell adhesion molecule Ovary Organic Chemistry Spheroid cell aggregation cell adhesion General Medicine medicine.disease Cell aggregation Computer Science Applications ovarian cancer medicine.anatomical_structure lcsh:Biology (General) lcsh:QD1-999 embryonic structures Cancer cell peptides Cancer research Nectin-4 Female Ovarian cancer Cell Adhesion Molecules Signal Transduction
Zdroj:	International Journal of Molecular Sciences, Vol 21, Iss 4637, p 4637 (2020) International Journal of Molecular Sciences Volume 21 Issue 13
ISSN:	1422-0067
DOI:	10.3390/ijms21134637
Popis:	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.
Databáze:	OpenAIRE
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