title: Apoptotic HPV positive cancer cells exhibit transforming properties.
abstract: Previous studies have shown that DNA can be transferred from dying engineered cells to neighboring cells through the phagocytosis of apoptotic bodies, which leads to cellular transformation. Here, we provide evidence of an uptake of apoptotic-derived cervical cancer cells by human mesenchymal cells. Interestingly, HeLa (HPV 18+) or Ca Ski (HPV16+) cells, harboring integrated high-risk HPV DNA but not C-33 A cells (HPV-), were able to transform the recipient cells. Human primary fibroblasts engulfed the apoptotic bodies effectively within 30 minutes after co-cultivation. This mechanism is active and involves the actin cytoskeleton. In situ hybridization of transformed fibroblasts revealed the presence of HPV DNA in the nucleus of a subset of phagocytosing cells. These cells expressed the HPV16/18 E6 gene, which contributes to the disruption of the p53/p21 pathway, and the cells exhibited a tumorigenic phenotype, including an increased proliferation rate, polyploidy and anchorage independence growth. Such horizontal transfer of viral oncogenes to surrounding cells that lack receptors for HPV could facilitate the persistence of the virus, the main risk factor for cervical cancer development. This process might contribute to HPV-associated disease progression in vivo.
authors.affiliation: Equipe d'Accueil 3181, Université de Franche-Comté, Besançon, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Gaiffe
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Prétet
authors.forename: Sophie
authors.initials: S
authors.lastname: Launay
authors.forename: Elise
authors.initials: E
authors.lastname: Jacquin
authors.forename: Maëlle
authors.initials: M
authors.lastname: Saunier
authors.forename: Geneviève
authors.initials: G
authors.lastname: Hetzel
authors.forename: Pierre
authors.initials: P
authors.lastname: Oudet
authors.forename: Christiane
authors.initials: C
authors.lastname: Mougin
mesh_terms: D017209:Apoptosis; D049109:Cell Proliferation; D002472:Cell Transformation, Viral / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000166:cytology; D005814:Genes, Viral / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D008648:Mesoderm / Q000166:cytology; D009857:Oncogenes / Q000235:genetics; D027383:Papillomaviridae / Q000235:genetics / Q000502:physiology*; D011123:Polyploidy; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000473:pathology*
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D016159:Tumor Suppressor Protein p53