The role of inflammation in HPV infection of the Oesophagus

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dc.contributor.authorSchäfer, Georgiaen_ZA
dc.contributor.authorKabanda, Sitien_ZA
dc.contributor.authorvan Rooyen, Beverlyen_ZA
dc.contributor.authorMarusic, Martina Berganten_ZA
dc.contributor.authorBanks, Lawrenceen_ZA
dc.contributor.authorParker, M Iqbalen_ZA
dc.date.accessioned2015-11-23T11:47:02Z
dc.date.available2015-11-23T11:47:02Z
dc.date.issued2013en_ZA
dc.description.abstractBACKGROUND: Several human cancers are known to be associated with inflammation and/or viral infections. However, the influence of tumour-related inflammation on viral uptake is largely unknown. In this study we used oesophageal squamous cell carcinoma (OSCC) as a model system since this type of cancer is associated with chronic irritation, inflammation and viral infections. Although still debated, the most important viral infection seems to be with Human Papillomavirus (HPV). The present study focused on a possible correlation between inflammation, OSCC development and the influence of HPV infection. METHODS: A total of 114 OSCC biopsies and corresponding normal tissue were collected at Groote Schuur Hospital and Tygerberg Hospital, Cape Town (South Africa), that were subjected to RNA and DNA isolation. RNA samples were analysed by quantitative Light Cycler RT-PCR for the expression of selected genes involved in inflammation and infection, while conventional PCR was performed on the DNA samples to assess the presence of integrated viral DNA. Further, an in vitro infection assay using HPV pseudovirions was established to study the influence of inflammation on viral infectivity using selected cell lines. RESULTS: HPV DNA was found in about 9% of OSCC patients, comprising predominantly the oncogenic type HPV18. The inflammatory markers IL6 and IL8 as well as the potential HPV receptor ITGA6 were significantly elevated while IL12A was downregulated in the tumour tissues. However, none of these genes were expressed in a virus-dependent manner. When inflammation was mimicked with various inflammatory stimulants such as benzo-alpha-pyrene, lipopolysaccharide and peptidoglycan in oesophageal epithelial cell lines in vitro, HPV18 pseudovirion uptake was enhanced only in the benzo-alpha-pyrene treated cells. Interestingly, HPV pseudovirion infectivity was independent of the presence of the ITGA6 receptor on the surface of the tested cells. CONCLUSION: This study showed that although the carcinogen benzo-alpha-pyrene facilitated HPV pseudovirion uptake into cells in culture, HPV infectivity was independent of inflammation and seems to play only a minor role in oesophageal cancer.en_ZA
dc.identifier.apacitationSchäfer, G., Kabanda, S., van Rooyen, B., Marusic, M. B., Banks, L., & Parker, M. I. (2013). The role of inflammation in HPV infection of the Oesophagus. <i>BMC Cancer</i>, http://hdl.handle.net/11427/15247en_ZA
dc.identifier.chicagocitationSchäfer, Georgia, Siti Kabanda, Beverly van Rooyen, Martina Bergant Marusic, Lawrence Banks, and M Iqbal Parker "The role of inflammation in HPV infection of the Oesophagus." <i>BMC Cancer</i> (2013) http://hdl.handle.net/11427/15247en_ZA
dc.identifier.citationSchäfer, G., Kabanda, S., Van Rooyen, B., Marušič, M. B., Banks, L., & Parker, M. I. (2013). The role of inflammation in HPV infection of the Oesophagus. BMC cancer, 13(1), 185.en_ZA
dc.identifier.ris TY - Journal Article AU - Schäfer, Georgia AU - Kabanda, Siti AU - van Rooyen, Beverly AU - Marusic, Martina Bergant AU - Banks, Lawrence AU - Parker, M Iqbal AB - BACKGROUND: Several human cancers are known to be associated with inflammation and/or viral infections. However, the influence of tumour-related inflammation on viral uptake is largely unknown. In this study we used oesophageal squamous cell carcinoma (OSCC) as a model system since this type of cancer is associated with chronic irritation, inflammation and viral infections. Although still debated, the most important viral infection seems to be with Human Papillomavirus (HPV). The present study focused on a possible correlation between inflammation, OSCC development and the influence of HPV infection. METHODS: A total of 114 OSCC biopsies and corresponding normal tissue were collected at Groote Schuur Hospital and Tygerberg Hospital, Cape Town (South Africa), that were subjected to RNA and DNA isolation. RNA samples were analysed by quantitative Light Cycler RT-PCR for the expression of selected genes involved in inflammation and infection, while conventional PCR was performed on the DNA samples to assess the presence of integrated viral DNA. Further, an in vitro infection assay using HPV pseudovirions was established to study the influence of inflammation on viral infectivity using selected cell lines. RESULTS: HPV DNA was found in about 9% of OSCC patients, comprising predominantly the oncogenic type HPV18. The inflammatory markers IL6 and IL8 as well as the potential HPV receptor ITGA6 were significantly elevated while IL12A was downregulated in the tumour tissues. However, none of these genes were expressed in a virus-dependent manner. When inflammation was mimicked with various inflammatory stimulants such as benzo-alpha-pyrene, lipopolysaccharide and peptidoglycan in oesophageal epithelial cell lines in vitro, HPV18 pseudovirion uptake was enhanced only in the benzo-alpha-pyrene treated cells. Interestingly, HPV pseudovirion infectivity was independent of the presence of the ITGA6 receptor on the surface of the tested cells. CONCLUSION: This study showed that although the carcinogen benzo-alpha-pyrene facilitated HPV pseudovirion uptake into cells in culture, HPV infectivity was independent of inflammation and seems to play only a minor role in oesophageal cancer. DA - 2013 DB - OpenUCT DO - 10.1186/1471-2407-13-185 DP - University of Cape Town J1 - BMC Cancer LK - https://open.uct.ac.za PB - University of Cape Town PY - 2013 T1 - The role of inflammation in HPV infection of the Oesophagus TI - The role of inflammation in HPV infection of the Oesophagus UR - http://hdl.handle.net/11427/15247 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/15247
dc.identifier.urihttp://dx.doi.org/10.1186/1471-2407-13-185
dc.identifier.vancouvercitationSchäfer G, Kabanda S, van Rooyen B, Marusic MB, Banks L, Parker MI. The role of inflammation in HPV infection of the Oesophagus. BMC Cancer. 2013; http://hdl.handle.net/11427/15247.en_ZA
dc.language.isoengen_ZA
dc.publisherBioMed Central Ltden_ZA
dc.publisher.departmentDivision of Medical Biochemistryen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an Open Access article distributed under the terms of the Creative Commons Attribution Licenseen_ZA
dc.rights.holder2013 Schäfer et al.; licensee BioMed Central Ltd.en_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/2.0en_ZA
dc.sourceBMC Canceren_ZA
dc.source.urihttp://www.biomedcentral.com/bmccancer/en_ZA
dc.subject.otherHPVen_ZA
dc.subject.otherCytokinesen_ZA
dc.subject.otherReceptorsen_ZA
dc.subject.otherOesophageal canceren_ZA
dc.titleThe role of inflammation in HPV infection of the Oesophagusen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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