Abstract
Optimal research results rely on the selection of cellular models capable of recapitulating the characteristics of primary tumours from which they originate. The expression of mucins (MUC16 and MUC1) and truncated O-glycans (Tn, STn and T) represents a characteristic footprint of serous ovarian carcinomas (SOCs). Therefore, selecting ovarian cancer (OVCA) cell lines that reflect this phenotype is crucial to explore the putative biological role of these biomarkers in the SOC setting. Here, we investigated a panel of OVCA cell lines commonly used as SOC models, and tested whether, when cultured in 2D and 3D conditions, these recapitulate the mucin and O-glycan expression profiles of SOCs. We further explored the role of truncating the O-glycosylation capacity in OVCAR3 cells through knockout of the COSMC chaperone, using in vitro and in vivo assays. We found that the majority of OVCA cell lines of serous origin do not share the mucin and truncated O-glycan footprint of SOCs, although 3D cultures showed a higher resemblance. We also found that genetic truncation of the O-glycosylation capacity of OVCAR3 cells did not enhance oncogenic features either in vitro or in vivo. This study underscores the importance of well-characterized cellular models to study specific features of ovarian cancer.
Highlights
Cancer cell lines have been used for decades as elective in vitro models in cancer research
A comparative study based on copy-number, mutations, and mRNA expression profiles revealed that most ovarian cancer (OVCA) cell lines widely used as serous ovarian carcinomas (SOCs) models do not reproduce the molecular features of serous origin [7]
We studied the expression of mucins MUC16 and MUC1 and truncated O-glycans Tn, STn and T by immunocytochemistry in eight OVCA cell lines derived from different peritoneal cavity sites, in 2D and 3D culture conditions (Figure 1A)
Summary
Cancer cell lines have been used for decades as elective in vitro models in cancer research. A comparative study based on copy-number, mutations, and mRNA expression profiles revealed that most OVCA cell lines widely used as SOC models do not reproduce the molecular features of serous origin [7] Another important aspect of in vitro cell models is the culture conditions, where 3D cell culture systems are widely accepted as more representative models that better reflect gene and protein expression patterns as well as microRNA and metabolic profiles of the tumours, as compared to 2D monolayer cultures [8,9]. We found that the majority of OVCA cell lines of serous origin do not express the characteristic mucin and O-glycan footprint of SOCs. we found that genetic truncation of O-glycosylation in OVCAR3 cells expressing MUC16 and MUC1 did not enhance oncogenic features in vitro or in vivo in xenografts. Our study underscores the importance of well-characterized cellular models to study specific features of ovarian tumours
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