Cells of Origin of Epithelial Ovarian Cancers

Abstract

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 stem/progenitor 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.

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Document Details

Document Type
Technical Report
Publication Date
Sep 01, 2015
Accession Number
AD1008130

Entities

People

  • Eunsil Park
  • Ying Xie
  • Zhe Li

Organizations

  • Brigham and Women's Hospital

Tags

DTIC Thesaurus Topics

  • Adenoviruses
  • Biomedical Research
  • Cancer
  • Cells
  • Department Of Defense
  • Epithelial Cells
  • Epithelium
  • Health Services
  • Medical Personnel
  • Neoplasms
  • Ovarian Cancer
  • Prostate Cancer
  • Reproductive System
  • Stem Cells
  • Viruses

Fields of Study

  • Biology

Readers

  • Molecular Biology and Genetics
  • Oncology
  • Oncology and Biomarker-Based Cancer Detection.

Technology Areas

  • Biotechnology
  • Biotechnology - Cancer Biotech
  • Space