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Although HCMV is not classically recognized as a cancer-causing virus, evidence suggests it may drive cancer development through its association with cancer hallmarks. This work shows that high-risk HCMV-DB and BL strains can trigger epithelial cell transformation by inducing polyploid giant cancer cells (PGCCs). The resulting transformed cells exhibit giant cell cycling with PGCC generation, dedifferentiation, stem-like features, and EMT. The proposed mechanism links PGCC cycling, increased EZH2 expression, EMT, and malignant traits to the cellular stress response caused by high-risk oncogenic HCMV, ultimately contributing to poor-prognosis adenocarcinoma.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/polyploid-giant-cancer-cells-a-distinctive-feature-in-the-transformation-of-epithelial-cells-by-high-risk-oncogenic-hcmv-strains/332405/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/polyploid-giant-cancer-cells-a-distinctive-feature-in-the-transformation-of-epithelial-cells-by-high-risk-oncogenic-hcmv-strains/332405.png","ImageObject",300,407,{"name":92,"@type":93},"Asher","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-23","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":29},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"How do high-risk HCMV strains influence epithelial cell transformation?","Question",{"text":112,"@type":113},"High-risk HCMV-DB and BL strains can trigger transformation in epithelial cells by inducing polyploid giant cancer cells (PGCCs). This is accompanied by a tumor-supportive cellular environment that promotes continued growth.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What cellular properties do the HCMV-transformed PGCC-related cells show?",{"text":117,"@type":113},"Transformed cells undergo giant cell cycling with PGCC generation parallel to dedifferentiation. They display stem-like characteristics and an epithelial–mesenchymal transition (EMT) phenotype.",{"name":119,"@type":110,"acceptedAnswer":120},"Why are PGCCs considered important in cancer progression and treatment response?",{"text":121,"@type":113},"PGCC abundance correlates with metastasis, resistance to chemoradiotherapy, and tumor recurrence. They are also discussed as stem-like, self-renewing cells and potential prognostic indicators.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},332405,1790875959,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":29,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":52,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144,"preview_page_count":4},687197207639,"https://ap-avatar.wpscdn.com/davatar_a8503ba1806abce46bf441b54a3ca4cd","viruses   \nReview  \nPolyploid Giant Cancer Cells: A Distinctive Feature in the Transformation of Epithelial Cells by High-Risk Oncogenic HCMV Strains  \nGeorges Herbein 1,2,* and Ranim El Baba 1  \nCitation: Herbein, G.; El Baba, R.  \nPolyploid Giant Cancer Cells: A Distinctive Feature in the Transformation of Epithelial Cells by High-Risk Oncogenic HCMV Strains. Viruses 2024, 16, 1225. [https://](https://)[ ](https://)[doi.org/10.3390/v16081225](doi.org/10.3390/v16081225)  \nAcademic Editor: Fenyong Liu  \nReceived: 14 May 2024  \nRevised: 26 July 2024  \nAccepted: 28 July 2024  \nPublished: 31 July 2024  \nCopyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Department Pathogens & Inflammation-EPILAB EA4266, University of Franche-Comté UFC,  \n25000 Besancon, France; [ranim.elbaba@live.com](ranim.elbaba@live.com)  \n2 Department of Virology, CHU Besançon, 250000 Besancon, France  \n* Correspondence: georges.herbein@univ-fcomte.fr or georges.herbein@gmail.com  \nAbstract: Human cytomegalovirus (HCMV) infection is common in tumor tissues across different types of cancer. While HCMV has not been recognized as a cancer-causing virus, numerous studies hint at its potential role in cancer development where its presence in various cancers corresponds with the hallmarks of cancer. Herein, we discuss and demonstrate that high-risk HCMV-DB and BL strains have the potential to trigger transformation in epithelial cells, including human mammary epithelial cells (HMECs), ovarian epithelial cells (OECs), and prostate epithelial cells (PECs), through the generation of polyploid giant cancer cells (PGCCs) . A discussion is provided on how HCMV infection creates a cellular environment that promotes oncogenesis, supporting the continuous growth of CMV-transformed cells. The aforementioned transformed cells, named CTH, CTO, and CTP cells, underwent giant cell cycling with PGCC generation parallel to dedifferentiation, displaying stem-like characteristics and an epithelial–mesenchymal transition (EMT) phenotype. Furthermore, we propose that giant cell cycling through PGCCs, increased EZH2 expression, EMT, and the acquisition of malignant traits represent a deleterious response to the cellular stress induced by high-risk oncogenic HCMV strains, the latter being the origin of the transformation process in epithelial cells upon HCMV infection and leading to adenocarcinoma of poor prognosis.  \nKeywords: human cytomegalovirus; high-risk oncogenic strains; epithelial cells; oncogenesis; CTH cells; CTO cells; CTP cells; PGCCs; giant cell cycling  \n1. Deciphering PGCCs in the Tumorigenic Landscape  \nPolyploid giant cancer cells (PGCCs) may possess either a single enlarged nucleus or multiple nuclei, denoted as mononucleated PGCCs or multinucleated PGCCs, respectively [1,2] . Initially, PGCCs were believed to arise solely from repeated failures in mitosis or cytokinesis, with limited proliferative potential; however, recent evidence has unveiled their resemblance to cancer stem cells (CSCs) [3] . PGCCs exhibit the ability to undergo asymmetric division, generating progeny cells expressing markers associated with epithelial–mesenchymal transition (EMT), thereby facilitating invasion and migration [4,5] . Various stimuli and stresses such as hypoxia, radiation, chemical drugs, viruses, and other stimuli that lead to DNA double-strand breaks can trigger PGCC formation [4] .  \nPGCCs manifest across a spectrum of malignant solid tumors, encompassing melanoma, urothelial carcinoma, renal cell carcinoma, breast and ovarian cancer, pancreatic carcinoma, prostate carcinoma [4,6–9], as well as hematologic malignancies such as leukemia [10,11] . The abundance of PGCCs corr","cbCaifm1YtzceWye","https://ap.wps.com/l/cbCaifm1YtzceWye","pdf",1377790,"English","# Abstract\n# 1. Deciphering PGCCs in the Tumorigenic Landscape\n## PGCC features and origins\n## Tumor types and clinical correlations\n## Therapeutic relevance\n# 2. Unveiling the Viral Culprit: HCMV Orchestrating Cancer Pathogenesis\n## HCMV–cancer relationship and oncogenic attention\n## Implicated roles in cancer pathogenesis","[{\"question\":\"How do high-risk HCMV strains influence epithelial cell transformation?\",\"answer\":\"High-risk HCMV-DB and BL strains can trigger transformation in epithelial cells by inducing polyploid giant cancer cells (PGCCs). This is accompanied by a tumor-supportive cellular environment that promotes continued growth.\"},{\"question\":\"What cellular properties do the HCMV-transformed PGCC-related cells show?\",\"answer\":\"Transformed cells undergo giant cell cycling with PGCC generation parallel to dedifferentiation. They display stem-like characteristics and an epithelial–mesenchymal transition (EMT) phenotype.\"},{\"question\":\"Why are PGCCs considered important in cancer progression and treatment response?\",\"answer\":\"PGCC abundance correlates with metastasis, resistance to chemoradiotherapy, and tumor recurrence. They are also discussed as stem-like, self-renewing cells and potential prognostic indicators.\"}]","Polyploid Giant Cancer Cells: A Distinctive Feature in the Transformation of Epithelial Cells by High-Risk Oncogenic HCMV Strains | PDF",1789998078,25]