Abstract 5752: Susceptibility of cells from cervical transformation zone to HPV-16 induced immortalization and dysplastic differentiation

Abstract

Abstract Persistent infection of high-risk human papillomavirus (HPV) is a major risk factor for cervical cancer. Greater than 90% of these cancers originate in the cervical transformation zone (CTZ), a narrow band of squamous metaplastic epithelium between ectocervix and endocervix. It is unclear why the CTZ has high susceptibility to malignant transformation and few studies have specifically examined cells from this region. We hypothesized cells cultured from human CTZ are uniquely susceptible to cellular immortalization and dysplastic differentiation, two alterations that contribute to malignant development. Primary epithelial cells were cultured from each region of human cervix (ectocervix, endocervix and CTZ) and characterized for expression of differentiation markers to assess their origin. We examined susceptibility of cells from each region to immortalization after transfection with the complete HPV-16 genome or infection of HPV-16 E6/E7 retroviruses. In addition, we evaluated the extent of dysplastic epithelial differentiation in organotypic cultures of HPV16-immortalized cell lines derived from each region of cervix. Our results showed that cells from the CTZ express specific keratin markers (keratin 14 and 18) that confirm their origin. Primary cell cultures from CTZ and ectocervix are more susceptible to immortalization by the HPV16 complete genome or E6/E7 retroviruses. In contrast, preliminary results indicate that HPV-immortalized CTZ and endocervical cells are more susceptible to dysplastic differentiation when maintained in organotypic culture. Our results may help to identify important signal pathways or biomarkers that are unique to cells from CTZ and that can be targeted for improved screening, prevention or therapy. Citation Format: Han Deng, Eric Hillpot, Philomina Yeboah, Sumona Mondal, Craig D. Woodworth. Susceptibility of cells from cervical transformation zone to HPV-16 induced immortalization and dysplastic differentiation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5752. doi:10.1158/1538-7445.AM2017-5752