Seminal plasma enhances cervical adenocarcinoma cell proliferation and tumour growth in vivo

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dc.contributor.authorSutherland, Jason Roberten_ZA
dc.contributor.authorSales, Kurt Jen_ZA
dc.contributor.authorJabbour, Henry Nen_ZA
dc.contributor.authorKatz, Arieh Aen_ZA
dc.date.accessioned2016-01-11T06:46:19Z
dc.date.available2016-01-11T06:46:19Z
dc.date.issued2012en_ZA
dc.description.abstractCervical cancer is one of the leading causes of cancer-related death in women in sub-Saharan Africa. Extensive evidence has shown that cervical cancer and its precursor lesions are caused by Human papillomavirus (HPV) infection. Although the vast majority of HPV infections are naturally resolved, failure to eradicate infected cells has been shown to promote viral persistence and tumorigenesis. Furthermore, following neoplastic transformation, exposure of cervical epithelial cells to inflammatory mediators either directly or via the systemic circulation may enhance progression of the disease. It is well recognised that seminal plasma contains an abundance of inflammatory mediators, which are identified as regulators of tumour growth. Here we investigated the role of seminal plasma in regulating neoplastic cervical epithelial cell growth and tumorigenesis. Using HeLa cervical adenocarcinoma cells, we found that seminal plasma (SP) induced the expression of the inflammatory enzymes, prostaglandin endoperoxide synthase (PTGS1 and PTGS2), cytokines interleukin (IL) -6, and -11 and vascular endothelial growth factor-A(VEGF-A). To investigate the role of SP on tumour cell growth in vivo, we xenografted HeLa cells subcutaneously into the dorsal flank of nude mice. Intra-peritoneal administration of SP rapidly and significantly enhanced the tumour growth rate and size of HeLa cell xenografts in nude mice. As observed in vitro, we found that SP induced expression of inflammatory PTGS enzymes, cytokines and VEGF-A in vivo. Furthermore we found that SP enhances blood vessel size in HeLa cell xenografts. Finally we show that SP-induced cytokine production, VEGF-A expression and cell proliferation are mediated via the induction of the inflammatory PTGS pathway.en_ZA
dc.identifier.apacitationSutherland, J. R., Sales, K. J., Jabbour, H. N., & Katz, A. A. (2012). Seminal plasma enhances cervical adenocarcinoma cell proliferation and tumour growth in vivo. <i>PLoS One</i>, http://hdl.handle.net/11427/16220en_ZA
dc.identifier.chicagocitationSutherland, Jason Robert, Kurt J Sales, Henry N Jabbour, and Arieh A Katz "Seminal plasma enhances cervical adenocarcinoma cell proliferation and tumour growth in vivo." <i>PLoS One</i> (2012) http://hdl.handle.net/11427/16220en_ZA
dc.identifier.citationSutherland, J. R., Sales, K. J., Jabbour, H. N., & Katz, A. A. (2012). Seminal plasma enhances cervical adenocarcinoma cell proliferation and tumour growth in vivo. PLoS One, 7(3), e33848. doi:10.1371/journal.pone.0033848en_ZA
dc.identifier.ris TY - Journal Article AU - Sutherland, Jason Robert AU - Sales, Kurt J AU - Jabbour, Henry N AU - Katz, Arieh A AB - Cervical cancer is one of the leading causes of cancer-related death in women in sub-Saharan Africa. Extensive evidence has shown that cervical cancer and its precursor lesions are caused by Human papillomavirus (HPV) infection. Although the vast majority of HPV infections are naturally resolved, failure to eradicate infected cells has been shown to promote viral persistence and tumorigenesis. Furthermore, following neoplastic transformation, exposure of cervical epithelial cells to inflammatory mediators either directly or via the systemic circulation may enhance progression of the disease. It is well recognised that seminal plasma contains an abundance of inflammatory mediators, which are identified as regulators of tumour growth. Here we investigated the role of seminal plasma in regulating neoplastic cervical epithelial cell growth and tumorigenesis. Using HeLa cervical adenocarcinoma cells, we found that seminal plasma (SP) induced the expression of the inflammatory enzymes, prostaglandin endoperoxide synthase (PTGS1 and PTGS2), cytokines interleukin (IL) -6, and -11 and vascular endothelial growth factor-A(VEGF-A). To investigate the role of SP on tumour cell growth in vivo, we xenografted HeLa cells subcutaneously into the dorsal flank of nude mice. Intra-peritoneal administration of SP rapidly and significantly enhanced the tumour growth rate and size of HeLa cell xenografts in nude mice. As observed in vitro, we found that SP induced expression of inflammatory PTGS enzymes, cytokines and VEGF-A in vivo. Furthermore we found that SP enhances blood vessel size in HeLa cell xenografts. Finally we show that SP-induced cytokine production, VEGF-A expression and cell proliferation are mediated via the induction of the inflammatory PTGS pathway. DA - 2012 DB - OpenUCT DO - 10.1371/journal.pone.0033848 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2012 T1 - Seminal plasma enhances cervical adenocarcinoma cell proliferation and tumour growth in vivo TI - Seminal plasma enhances cervical adenocarcinoma cell proliferation and tumour growth in vivo UR - http://hdl.handle.net/11427/16220 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/16220
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0033848
dc.identifier.vancouvercitationSutherland JR, Sales KJ, Jabbour HN, Katz AA. Seminal plasma enhances cervical adenocarcinoma cell proliferation and tumour growth in vivo. PLoS One. 2012; http://hdl.handle.net/11427/16220.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentMRC/UCT Receptor Biology Research Groupen_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 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_ZA
dc.rights.holder© 2012 Sutherland et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plosoneen_ZA
dc.subject.otherHeLa cellsen_ZA
dc.subject.otherInflammationen_ZA
dc.subject.otherCancer treatmenten_ZA
dc.subject.otherCytokinesen_ZA
dc.subject.otherGene expressionen_ZA
dc.subject.otherBlood plasmaen_ZA
dc.subject.otherMouse modelsen_ZA
dc.subject.otherCervical canceren_ZA
dc.titleSeminal plasma enhances cervical adenocarcinoma cell proliferation and tumour growth in vivoen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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