The role of seminal plasma in the regulation of inflammation and inflammatory pathways in the cervix: potential for cervical cancer progression and HIV transmission in South African women

Doctoral Thesis

2014

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University of Cape Town

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Cervical cancer is a chronic inflammatory disease of multifactorial etiology accounting for an annual estimated 266,000 deaths worldwide and usually present in sexually active women. In sub-Saharan Africa, cervical cancer is the most common cancer among women and the leading cause of cancer related deaths in this region. The obvious association of HIV infection and cervical cancer has long been established. High incidence and prevalence rate of HIV infection has been recorded in many areas with high incidence of cervical cancer suggesting that cervical cancer and premalignant cervical lesions may increase transmission and acquisition of HIV infection. Seminal plasma (SP) has been shown to initiate inflammatory response within the female genital tract. Exposure of neoplastic cervical epithelial cells to SP has been shown to promote the growth of cancer cells in vitro and tumors in vivo by activating several proinflammatory pathways. In addition to the regulation of tumor growth, SP-mediated inflammatory responses within the female genital tract have been suggested to contribute to the transmission of HIV and other sexually transmitted infections (STIs). The initial aim of this study was to determine the role of SP in the regulation of proinflammatory pathways in neoplastic cervical epithelial cells. TaqMan 96-well array revealed that SP regulates the activation of eicosanoid, toll-like receptor-NFκB, kallikrien-bradykininbradykinin receptor, cytokine, and chemokine signaling pathways to mediate the expression of inflammatory mediators in cervical cancer cells. These data highlight the potential of SP to exacerbate inflammatory processes within the local cervical cancer microenvironment creating conditions favorable for cervical tumor progression.
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