Ovarian surface epithelium at the junction area contains a cancer-prone stem cell niche

Flesken-Nikitin, A., Hwang, C. I., Cheng, C. Y., Michurina, T. V., Enikolopov, G., Nikitin, A. Yu (March 2013) Ovarian surface epithelium at the junction area contains a cancer-prone stem cell niche. Nature, 495 (7440). pp. 241-5. ISSN 00280836 (ISSN)

URL: http://www.ncbi.nlm.nih.gov/pubmed/23467088
DOI: 10.1038/nature11979

Abstract

Epithelial ovarian cancer (EOC) is the fifth leading cause of cancer deaths among women in the United States, but its pathogenesis is poorly understood. Some epithelial cancers are known to occur in transitional zones between two types of epithelium, whereas others have been shown to originate in epithelial tissue stem cells. The stem cell niche of the ovarian surface epithelium (OSE), which is ruptured and regenerates during ovulation, has not yet been defined unequivocally. Here we identify the hilum region of the mouse ovary, the transitional (or junction) area between the OSE, mesothelium and tubal (oviductal) epithelium, as a previously unrecognized stem cell niche of the OSE. We find that cells of the hilum OSE are cycling slowly and express stem and/or progenitor cell markers ALDH1, LGR5, LEF1, CD133 and CK6B. These cells display long-term stem cell properties ex vivo and in vivo, as shown by our serial sphere generation and long-term lineage-tracing assays. Importantly, the hilum cells show increased transformation potential after inactivation of tumour suppressor genes Trp53 and Rb1, whose pathways are altered frequently in the most aggressive and common type of human EOC, high-grade serous adenocarcinoma. Our study supports experimentally the idea that susceptibility of transitional zones to malignant transformation may be explained by the presence of stem cell niches in those areas. Identification of a stem cell niche for the OSE may have important implications for understanding EOC pathogenesis.

Item Type: Paper
Subjects: diseases & disorders > cancer
diseases & disorders
organs, tissues, organelles, cell types and functions > cell types and functions > cell types
organs, tissues, organelles, cell types and functions > cell types and functions > cell types
organs, tissues, organelles, cell types and functions > cell types and functions > cell types

organs, tissues, organelles, cell types and functions > cell types and functions
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > epithelial cell
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > epithelial cell
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > epithelial cell

diseases & disorders > cancer > cancer types > ovarian cancer
diseases & disorders > cancer > cancer types
CSHL Authors:
Communities: CSHL Cancer Center Shared Resources > Animal Services
CSHL Cancer Center Shared Resources > Microscopy Service
CSHL labs > Enikopolov lab
CSHL Cancer Center Program > Signal Transduction
Depositing User: Matt Covey
Date: 14 March 2013
Date Deposited: 29 Mar 2013 13:05
Last Modified: 16 Oct 2015 13:57
Related URLs:
URI: http://repository.cshl.edu/id/eprint/28059

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