Department Pathogens & Inflammation-EPILAB EA4266, University of Bourgogne France-Comté, Besançon, France.
Lebanese University, Beyrouth, Lebanon.
Oncogene. 2021 Apr;40(17):3030-3046. doi: 10.1038/s41388-021-01715-7. Epub 2021 Mar 25.
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.
越来越多的证据将人类巨细胞病毒（HCMV）确认为一种潜在的致癌病毒。通过诱导成熟人乳腺上皮细胞（HMEC）去分化，产生具有胚裂样细胞持续生长特征的多倍体巨大癌细胞（PGCC）表型，我们在此提供了 HCMV 作为重编程载体的首个体外实验证据，这与获得胚胎干细胞特征和上皮-间充质可塑性一致。HCMV 的存在与观察到的细胞和分子事件的相继发生，可能是转化过程的后续事件。在乳腺癌组织中 PGCC 的检测与 HCMV 存在之间的相关性进一步验证了我们在体内的假设。我们的研究表明，一些临床 HCMV 株具有转化 HMEC 的潜力，符合“胚裂样”致癌模型，这可能与乳腺癌和其他腺癌的病理生理学有关，尤其是预后不良的病例。
