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Int. J. Mol. Sci. 2018, 19(7), 2045; https://doi.org/10.3390/ijms19072045

Mucins and Truncated O-Glycans Unveil Phenotypic Discrepancies between Serous Ovarian Cancer Cell Lines and Primary Tumours

1
Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, 4099-002 Porto, Portugal
2
Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4099-002 Porto, Portugal
3
Faculty of Medicine, University of Porto, 4099-002 Porto, Portugal
4
Instituto de Biologia Experimental e Tecnológica (iBET), 2780-901 Oeiras, Portugal
5
Instituto de Tecnologia Química e Biológica (ITQB) António Xavier, Universidade Nova de Lisboa, 2780-157 Oeiras, Portugal
6
Glyco-Oncology, Ovarian Cancer Research, Department of Biomedicine, University Hospital Basel and University of Basel, 4031 Basel, Switzerland
7
Copenhagen Center for Glycomics, Department of Odontology, Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark
Present work address: Portsmouth Hospitals NHS Trust, United Kingdom.
*
Author to whom correspondence should be addressed.
Received: 18 June 2018 / Revised: 5 July 2018 / Accepted: 10 July 2018 / Published: 13 July 2018
(This article belongs to the Special Issue Ovarian Cancer: Pathogenesis, Diagnosis, and Treatment)
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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. View Full-Text
Keywords: serous ovarian carcinomas; ovarian cancer cell lines; MUC16; MUC1; truncated O-glycans; COSMC serous ovarian carcinomas; ovarian cancer cell lines; MUC16; MUC1; truncated O-glycans; COSMC
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Coelho, R.; Marcos-Silva, L.; Mendes, N.; Pereira, D.; Brito, C.; Jacob, F.; Steentoft, C.; Mandel, U.; Clausen, H.; David, L.; Ricardo, S. Mucins and Truncated O-Glycans Unveil Phenotypic Discrepancies between Serous Ovarian Cancer Cell Lines and Primary Tumours. Int. J. Mol. Sci. 2018, 19, 2045.

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