A growing body of evidence is recognizing human cytomegalovirus (HCMV) as a potential oncogenic virus. We hereby provide the first experimental in vitro evidence for HCMV as a reprogramming vector, through the induction of dedifferentiation of mature human mammary epithelial cells (HMECs), generation of a polyploid giant cancer cell (PGCC) phenotype characterized by sustained growth of blastomere-like cells, in concordance with the acquisition of embryonic stem cells characteristics and epithelial-mesenchymal plasticity. HCMV presence parallels the succession of the observed cellular and molecular events potentially ensuing the transformation process. Correlation between PGCCs detection and HCMV presence in breast cancer tissue further validates our hypothesis in vivo. Our study indicates that some clinical HCMV strains conserve the potential to transform HMECs and fit with a “blastomere-like” model of oncogenesis, which may be relevant in the pathophysiology of breast cancer and other adenocarcinoma, especially of poor prognosis.
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The data supporting the findings of this study are available within the article and its Supplementary Information files and from the corresponding authors on request.
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This work was supported by grants from the University of Franche-Comté, and the Région Franche-Comté. Z.N. is a recipient of a doctoral scholarship from the municipality of Habbouch. The funders had no role in the data collection, analysis, patient recruitment, or decision to publish. We thank DImaCell Imaging Ressource Center, University of Bourgogne Franche-Comté, Faculty of Health Sciences, 25000 Besançon, France for technical support.
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Nehme, Z., Pasquereau, S., Haidar Ahmad, S. et al. Polyploid giant cancer cells, stemness and epithelial-mesenchymal plasticity elicited by human cytomegalovirus. Oncogene 40, 3030–3046 (2021). https://doi.org/10.1038/s41388-021-01715-7