Abstract 2442: Seminal fluid enhances cervical squamous carcinoma cell proliferation, epithelial mesenchymal transition (EMT), migration & invasion

Abstract

Abstract Cervical cancer is the leading cause of cancer related deaths & the second most common cancer amongst South African women. Though there are various risk factors, the most common risk factor for cervical cancer development is sexual transmission & persistent infection with high-risk Human Papillomavirus (HPV). Although most HPV infections are cleared naturally in women, persistent infection with high-risk HPV types promotes neoplastic transformation & tumorigenesis. Furthermore, exposure of neoplastic cervical epithelial cells to inflammatory mediators may drive the progression of cervical cancer. Seminal fluid (SF), a biological fluid rich in inflammatory mediators & growth factors, has been implicated in cervical cancer progression. SF has been shown to induce the expression of proinflammatory mediators which promotes cell proliferation in culture & growth of explants in mice injected with HeLa cervical adenocarcinoma cells. Since majority of cervical cancer cases are squamous cell carcinoma, in this study, we examined the effect of SF on cell proliferation, EMT, cell migration & invasion employing SiHa and Me180 squamous cell carcinoma cell lines. Our results showed that SF significantly enhanced cell proliferation in both cell lines. Using Confocal microscopy and phalloidin staining we further showed that SF caused morphological changes and stress fibre formation. RT-qPCR showed that SF up regulated EMT transcription factors Snail, ZEB1 & TWIST mRNA expression. EMT induction was further confirmed by the increase of N-cadherin & a subsequent decrease in E-cadherin protein expression. Additionally, we showed that the induction of EMT transcription factors by SF occurs via the EGF/ERK/COX pathway. To investigate the effect of SF on migration and invasion, transwell migration assays were used. Results showed that SF significantly enhanced cell migration & invasion of the SiHa and Me180 cells. Our results show that SF plays a role in enhancing the migratory & invasive potential of squamous cell carcinoma cells & that this associates with increased expression of EMT transcription factors. These findings together implicate SF as a possible factor that may promote cervical cancer progression. Citation Format: Nonkululeko Mkwanazi, Virna D. Leaner, Arieh A. Katz. Seminal fluid enhances cervical squamous carcinoma cell proliferation, epithelial mesenchymal transition (EMT), migration & invasion [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2442.