期刊
ONCOGENE
卷 29, 期 8, 页码 1103-1113出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2009.402
关键词
ovarian cancer; fallopian tube; primary cell culture; cancer biomarkers; DNA damage and repair
资金
- National Cancer Institute [P50 CA105009, K08 CA108748, R21 CA124688]
- Ovarian Cancer Research Fund
- Phi Beta Psi Sorority Charitable Trust
- Fannie E. Ripple Foundation
- Robert and Deborah First Fund
- Randi and Joel Cutler Ovarian Cancer Research Fund
- Columbia Hospital for Women Research Foundation
- Marsha Rivkin Foundation Scientific Scholar Award
- AACR-George and Patricia Sehl Fellowship
- American Physicians Fellowship
- Emmanuel G Rosenblatt Foundation
Recent studies suggest that some serous ovarian carcinomas (SOCs) arise from the fallopian tube (FT) epithelium rather than the ovarian surface epithelium. This hypothesis places emphasis on the FT secretory epithelial cell as a cell-of-origin. Herein, we report the development of a novel ex vivo primary human FT epithelium culture system that faithfully recapitulates the in vivo epithelium, as shown by morphological, ultrastructural and immunophenotypic analyses. Mass spectrometry-based proteomics reveal that these cultures secrete proteins previously identified as biomarkers for ovarian cancer. We also use this culture system to study the response of the FT epithelium to genotoxic stress and find that the secretory cells exhibit a distinct response to DNA damage when compared with neighboring ciliated cells. The secretory cells show a limited ability to resolve the damage over time, potentially leaving them more susceptible to 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 FT epithelial pathobiology. We anticipate that this novel culture system will facilitate the study of SOC pathogenesis, and propose that similar culture systems could be developed for other organ site-specific epithelia. Oncogene (2010) 29, 1103-1113; doi: 10.1038/onc.2009.402; published online 23 November 2009
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