Stem cell activity in the outer lining of the ovary, now identified in mice by A*STAR researchers, will elucidate normal ovarian activity and offer insights into the origins of disease.
Ovarian cancer kills more than 150,000 women globally each year, but the molecular and cellular events behind it remain unclear. "We need to understand the normal cell biology of the ovary before we can begin to understand what goes wrong during cancer, for example," says Nick Barker of the A*STAR team.
At the A*STAR Institute of Medical Biology, Barker and his team studied the regeneration and repair of the surface cell layer—the epithelium—of the ovary and fallopian tube, along with collaborators at the National University of Singapore. During ovulation this crucial layer of cells undergoes repeated cycles of tearing and subsequent repair (see image). Little is known, however, about the molecular mechanism of the tissue renewal process, or how it is disrupted during disease.
Resident stem cells drive such tissue maintenance activities in many epithelial layers throughout the body, explains Barker, but similar stem cells have never been proven to exist in the ovary.
Previous work by Barker and his colleagues had shown that a cell-surface receptor protein, known as Lgr5, acts as a marker identifying stem cells in various epithelial layers, including those of the intestine, stomach and kidney.
The most recent work has identified the protein on cells of the ovaries and fallopian tubes of mice which confirms the presence and activity of resident stem cells that can maintain the ovarian epithelium.
"This will give scientists the ability to decipher the biology of these stem cells in normal healthy tissue," comments Barker. He explains that mutations in stem cells are likely to be a major cause of cancers of the ovarian epithelium. This is highly probable, he says, given that the Lgr5-bearing stem cells identified by his previous work are a major source of epithelial cancers of the stomach and intestine.
Next Barker and his team plan to create targeted mutations in specific genes and analyze the possible role of these mutations in ovarian cancer. They also hope to build on the work with mice by purifying and growing human ovarian stem cells and epithelia in culture, providing insights that will be directly relevant to medical applications.
"This basic research is a prerequisite for eventually being able to develop more targeted and more effective therapies to treat ovarian disease," says Barker.
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Annie Ng et al. Lgr5 marks stem/progenitor cells in ovary and tubal epithelia, Nature Cell Biology (2014). DOI: 10.1038/ncb3000