Embryonic pathway delivers stem cell traits

As he pondered these findings and the earlier results about FOXC2’s 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 Texas’s M. D. Anderson Cancer Center in Houston. “He said, ‘You must be out of your mind, but it won’t take more than half an hour to check.’”

Much to Liao’s 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 mammospheres—another trait of mammary stem cells. Some cells in the resulting mammospheres showed, in turn, stem cell markers, indicating they could differentiate into two kinds of mammary cells. And cells in the mammospheres retained their stem cell properties even after the EMT induction process was stopped.

Furthermore, when the Weinberg lab scientists isolated stem-cell-like cells from cultured human mammary epithelial cells or from mouse breast tissue, their properties were very similar to the EMT-induced cells. Working with Kornelia Polyak of Dana-Farber Cancer Institute and Harvard Medical School, Mani found that this was also true with normal and tumor cells obtained from human patients.

“This for us is a very exciting discovery, not only because of its unexpectedness but because it offers a route by which one could in principle generate unlimited numbers of stem cells committed to create a specific cell type,” says Weinberg, who is also a professor of biology at Massachusetts Institute of Technology. “One could imagine, for example, that if one takes skin cells and induces them to undergo an EMT, they could become skin stem cells.”

Importantly, the researchers also demonstrated that inducing the EMT process can produce cells with many characteristics of cancer stem cells. (Beginning in 2003, scientists in various labs have identified these self-renewing, tumor-seeding cells in a number of solid tumors.)

This finding could help to answer a key question about metastasis: When tumor cells spread into different sites, how do they multiply enough to form a dangerous new tumor"