Mani knew that during embryonic development, FOXC2 expression is restricted to mesoderm and mesoderm-derived cells when they are in an undifferentiated state, and its expression disappears once these cells differentiate. Similarly, his experiments showed that epithelial cells that undergo EMT express FOXC2, but that expression is lost when they revert back to an epithelial state.
In collaboration with Andrea Richardson and Jeffery Kutok, pathologists at Bostons Brigham and Womens Hospital, Mani went on to study FOXC2 expression in normal human breast tissue. It turned out that such cells were located precisely where researchers expect to find mammary epithelial stem cells.
As he pondered these findings and the earlier results about FOXC2s role in metastasis, Mani wondered: Just what were these cells generated by EMT that expressed FOXC2"
Were they simply fibroblasts, the most common cells in normal connective tissue" Or were they actually stem cells"
I asked Mai-Jing Liao, another postdoc in the Weinberg lab, to check whether the cells generated by EMT would have any stem cell properties, recalls Mani, now an assistant professor in the department of molecular pathology at the University of Texass M. D. Anderson Cancer Center in Houston. He said, You must be out of your mind, but it wont take more than half an hour to check.
Much to Liaos surprise, when he examined cells that had undergo an EMT, his tests did highlight surface proteins that are key markers for stem cells.
The researchers found that the cells that underwent the EMT process were mesenchymal-like in appearance and demonstrated stem-cell surface markers. The cells also displayed an increased ability to grow in suspension, forming structures called mammospheresanother trait of mammary stem cells. Some cells in the resulting mammospheres showed, in turn, stem cell markers, indicating they could differ
|Contact: Cristin Carr|
Whitehead Institute for Biomedical Research