CCR5 expression is elevated in cervical cancer cells and is up-regulated by seminal plasma

The interplay between inflammation, cervical cancer and HIV acquisition in women is poorly understood. We have previously shown that seminal plasma (SP) can promote cervical tumour cell growth in vitro and in vivo via the activation of potent inflammatory pathways. In this study, we investigated whether SP could regulate expression of chemokine receptors with known roles in HIV infection, in the cervix and in cervical cancer. The expression of CD4 and CCR5 was investigated by RT-PCR analysis and immunohistochemistry. CD4 and CCR5 expression was elevated in cervical cancer tissue compared with normal cervix. Ex vivo studies conducted on cervical tissues and HeLa cells showed that SP significantly increases the expression of CD4 and CCR5 transcripts. Furthermore, it was found that SP also up-regulates CCR5 protein in HeLa cells. The regulation of CCR5 expression was investigated following treatment of HeLa cells with SP in the presence/absence of chemical inhibitors of intracellular signalling, EP2 and EP4 antagonists, prostaglandin (PG) E2 and a cyclooxygenase (COX)-1 doxycycline-inducible expression system. These experiments demonstrated that the regulation of CCR5 expression by SP occurs via the epidermal growth factor receptor (EGFR)-COX-1-PGE2 pathway. This study provides a link between activation of inflammatory pathways and regulation of HIV receptor expression in cervical cancer cells.