Apoptotic HPV positive cancer cells exhibit transforming properties.

PloS One
Emilie GaiffeChristiane Mougin

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-as...Continue Reading

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Citations

Oct 1, 2014·Journal of Experimental & Clinical Cancer Research : CR·Mohamed AbdouhGoffredo Arena
Jan 4, 2013·PloS One·Catalina Trejo-BecerrilAlfonso Dueñas-González
May 6, 2016·Integrative Cancer Therapies·Catalina Trejo-BecerrilAlfonso Dueñas-González
Sep 25, 2017·Journal of Circulating Biomarkers·Mohamed AbdouhGoffredo Orazio Arena
Jan 10, 2018·Frontiers in Immunology·Niloofar Karaji, Quentin J Sattentau
May 1, 2020·Journal of Biomolecular Structure & Dynamics·Raied A BadierahElrashdy M Redwan
May 18, 2016·Journal of Experimental & Clinical Cancer Research : CR·Dana HamamGoffredo Orazio Arena
Sep 1, 2017·Journal of Experimental & Clinical Cancer Research : CR·Mohamed AbdouhGoffredo Orazio Arena

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Methods Mentioned

BETA
confocal microscopy
flow cytometry
PCR
genetic modifications
electrophoresis
genotyping
scraping
PCRs

Software Mentioned

[UNK]
cytometer

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