Cells of Origin of Epithelial Ovarian Cancers
Technical Report,15 Aug 2014,14 Aug 2015
THE BRIGHAM AND WOMEN'S HOSPITAL, INC. BOSTON United States
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Epithelial ovarian cancer EOC is the most lethal malignancy of the female reproductive system, largely due to the fact that most EOCs are diagnosed only after the cancer has metastasized into the peritoneal space of the patient. Thus, a better understanding of the cellular origin and early stages of EOC will have important implications for prevention and early diagnosis of EOC. Both ovarian surface epithelial and fallopian tubal epithelial cells have been proposed as cells of origin of EOC. To determine cellular origin of EOC and to test whether different oncogenic events contribute to different subtypes of EOC, we utilize Cre-expressing adenovirus under the control of a keratin 8 K8 promoter Ad-K8-Cre to initiate oncogenic events in K8 ovarian surface epithelial and fallopian tubal epithelial cells, coupled with lineage-tracing. By immunostaining and flow cytometric analyses, we found that K8 is expressed in ovarian surface epithelial and fallopian tubal epithelial cells and its expression correlates with that of Lgr5, a marker of ovary and tubal epithelial stemprogenitor cells. Intrabursal injection of Ad-K8-Cre to Rosa26-STOP-YFP reporter mice leads to genetic marking of two subpopulations of epithelial cells in both ovary and fallopian tube, which overlap with the Lgr5 subpopulations. Currently our effort focuses on targeting the K8 population for EOC initiation.