Cornell University researchers have discovered a novel stem cell niche for the ovarian surface epithelium in mice and showed that ovarian carcinoma preferentially originates from stem cells found in that niche.
This stem cell niche lies in a transitional area known as the hilum region, a layer of cells that links the ovary to the rest of the body.
Some epithelial cancers are known to occur in transitional zones between two types of epithelium (layers of tissue that line the body and organs and form glands), while others originate in epithelial tissue stem cells.
All organs have the capacity for regeneration, which is done by adult stem cells located in areas of each organ called stem cell niches.
"We now know where these cells are located in mice, so we can look in humans in those areas," said Alexander Nikitin, senior author of the paper published in journal Nature.
The researchers proved that stem cells from the hilum region were highly prone to ovarian carcinoma, using the most current genetic research techniques.
The researchers first found that cells in the hilum region express a known marker for stem cells, called ALDH1. They then isolated ALDH1 positive cells, sequenced their genetic profiles and found many markers previously reported for stem cells in other organs.
One of these markers, LGR5, has been studied for intestinal stem cells by other researchers who have bred special mice and developed an advanced method that uses a fluorescent protein to follow stem cells.
The gene encoding the fluorescent protein is passed down from a stem cell to each generation of daughter cells, thereby marking the lineage.
The technique "allows you to see the fate of stem cells over time," said Nikitin. Using the method on the hilum cells, "we showed that cells from the hilum area spread around the whole ovary."
Finally, the researchers microdissected ovary and hilum cells, inactivated two tumour suppressor genes p53 and Rb1, whose pathways are commonly altered in human aggressive ovarian carcinoma, and injected cells into the abdominal cavity of mice.
Very few tumours developed in the mice injected with ovary cells, but almost all of the mice injected with hilum cells died after developing aggressive, metastasising cancers that were similar to human ovarian carcinomas.