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Multicellular Human Gastric Cancer Spheroids Mimic the Glycosylation Phenotype of Gastric Carcinomas

i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal
IPATIMUP-Institute of Molecular Pathology and Immunology, University of Porto, 4200-135 Porto, Portugal
INEB-Instituto de Engenharia Biomédica, University of Porto, 4200-135 Porto, Portugal
Institute of Biomedical Sciences of Abel Salazar–ICBAS, University of Porto, 4050-313 Porto, Portugal
Medical Faculty, University of Porto, 4200-319 Porto, Portugal
Author to whom correspondence should be addressed.
Academic Editors: Franz-Georg Hanisch and Isabelle Breloy
Molecules 2018, 23(11), 2815;
Received: 28 September 2018 / Revised: 19 October 2018 / Accepted: 25 October 2018 / Published: 30 October 2018
(This article belongs to the Special Issue Functional Roles of Protein O-Glycosylation)
PDF [3384 KB, uploaded 31 October 2018]


Cellular glycosylation plays a pivotal role in several molecular mechanisms controlling cell–cell recognition, communication, and adhesion. Thus, aberrant glycosylation has a major impact on the acquisition of malignant features in the tumor progression of patients. To mimic these in vivo features, an innovative high-throughput 3D spheroid culture methodology has been developed for gastric cancer cells. The assessment of cancer cell spheroids’ physical characteristics, such as size, morphology and solidity, as well as the impact of glycosylation inhibitors on spheroid formation was performed applying automated image analysis. A detailed evaluation of key glycans and glycoproteins displayed by the gastric cancer spheroids and their counterpart cells cultured under conventional 2D conditions was performed. Our results show that, by applying 3D cell culture approaches, the model cell lines represented the differentiation features observed in the original tumors and the cellular glycocalix underwent striking changes, displaying increased expression of cancer-associated glycan antigens and mucin MUC1, ultimately better simulating the glycosylation phenotype of the gastric tumor. View Full-Text
Keywords: 3D cell culture; gastric cancer; glycosylation; MUC1; spheroids; swainsonine; tunicamycin 3D cell culture; gastric cancer; glycosylation; MUC1; spheroids; swainsonine; tunicamycin

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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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Balmaña, M.; Mereiter, S.; Diniz, F.; Feijão, T.; Barrias, C.C.; Reis, C.A. Multicellular Human Gastric Cancer Spheroids Mimic the Glycosylation Phenotype of Gastric Carcinomas. Molecules 2018, 23, 2815.

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