Primary ex vivo cultures of human fallopian tube epithelium as a model for serous ovarian carcinogenesis

Abstract

Recent studies suggest that some serous ovarian carcinomas arise from the fallopian tube epithelium rather than the ovarian surface epithelium. This hypothesis places emphasis on the fallopian tube secretory epithelial cell as a cell-of-origin. Herein we report the development of a novel ‘ex-vivo’ primary human fallopian tube epithelium culture system that faithfully recapitulates the in-vivo epithelium, as demonstrated by morphological, ultrastructural, and immunophenotypic analyses. Mass spectrometry-based proteomics reveals that these cultures secrete proteins previously identified as biomarkers for ovarian cancer. We also utilize this culture system to study the response of the fallopian tube epithelium to genotoxic stress and find that the secretory cells exhibit a distinct response to DNA damage when compared to neighboring ciliated cells. The secretory cells demonstrate a limited ability to resolve the damage over time, potentially leaving them more susceptible accumulation of additional mutagenic injury. This divergent response is confirmed with in-situ studies using tissue samples, further supporting the use of this ex-vivo culture system to investigate fallopian tube epithelial pathobiology. We anticipate that this novel culture system will facilitate the study of serous ovarian carcinoma pathogenesis, and propose that similar culture systems could be developed for other organ-site specific epithelia.