Polyploid Giant Cancer Cells Generated from Human Cytomegalovirus-Infected Prostate Epithelial Cells

SIMPLE SUMMARY: Prostate cancer remains a leading cause of death in men worldwide. Polyploid giant cancer cells (PGCCs) and chromosomal instability have been proposed to drive the progression of cancer. Given that HCMV infection has been implicated in malignant diseases from different cancer entities, in the present study, we assessed its transformation potential in vitro and evaluated the obtained cellular and molecular phenotypes of prostate epithelial cells (PECs) using HCMV high-risk clinical strains, DB and BL, which were previously isolated in our laboratory. HCMV-induced PGCC formation, Myc and EZH2 upregulation, as well as the stemness and epithelial–mesenchymal transition features verified the transformation process of PECs. Our research work deserves to be distributed among the scientific community, as it paves the way for upcoming studies targeting the potential role of HCMV and PGCCs in prostate cancer development and treatment. ABSTRACT: Background: Prostate cancer is the most commonly diagnosed malignancy and the sixth leading cause of cancer death in men worldwide. Chromosomal instability (CIN) and polyploid giant cancer cells (PGCCs) have been considered predominant hallmarks of cancer. Recent clinical studies have proven the association of CIN, aneuploidy, and PGCCs with poor prognosis of prostate cancer (PCa). Evidence of HCMV transforming potential might indicate that HCMV may be involved in PCa. Methods: Herein, we underline the role of the high-risk HCMV-DB and -BL clinical strains in transforming prostate epithelial cells and assess the molecular and cellular oncogenic processes associated with PCa. Results: Oncogenesis parallels a sustained growth of “CMV-Transformed Prostate epithelial cells” or CTP cells that highly express Myc and EZH2, forming soft agar colonies and displaying stemness as well as mesenchymal features, hence promoting EMT as well as PGCCs and a spheroid appearance. Conclusions: HCMV-induced Myc and EZH2 upregulation coupled with stemness and EMT traits in IE1-expressing CTP might highlight the potential role of HCMV in PCa development and encourage the use of anti-EZH2 and anti-HCMV in PCa treatment.