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Adult Cells Steal Trick from Cancer to Become Stem Cell-Like

A route used by tumor cells to spread could be exploited to make stem cells for regenerative medicine and cancer therapies
mesenchymal cells



COURTESY OF SENDURAI MANI

In a boon to cancer treatment and regenerative medicine, scientists have discovered that a trick used by tumor cells that allows them to migrate around the body can cause normal, adult cells to revert into stem cell–like cells.

Large quantities of these reverted cells could be used to treat anything from spinal cord injury to liver damage without the risk of tissue rejection, said Robert Weinberg, a biologist at the Massachusetts Institute of Technology's Whitehead Institute for Biomedical Research and co-author of a study appearing in Cell. Learning more about how cancer cells move around the body is also providing scientists with new insights that could thwart the spread of the disease.

The key to the process is a better understanding of developmental changes in the body’s two primary cell types: epithelial cells (those that constitute the skin and most internal organs) and mesenchymal cells (which make up connective tissue). The key difference between the two cell categories is that epithelial cells adhere very tightly to one another, making sheetlike layers, whereas mesenchymal cells are only loosely bound and can migrate within the body. In the developing embryo, an initial group of epithelial cells undergoes a shift called an "epithelial to mesenchymal transition" (EMT) to form bones, blood and cartilage as well as the heart.

Likewise, some cancerous cells can perform a temporary EMT transformation to the mobile mesenchymal form. The conversion improves the cells' tumor-forming ability, cutting the number of tumor cells required to form a carcinoma from one million to just 10,000, the researchers say.

"More than 80 percent of cancer in humans occurs in epithelial cells," says study co-author Sendurai Mani, an assistant professor of molecular pathology at the University of Texas' M.D. Anderson Cancer Center in Houston and a former postdoc in Weinberg's lab. Previous work in Weinberg's lab had shown that after a tumor forms in one part of the body, some of the cancer cells undergo EMT, Mani explains. The now-mesenchymal cells can then travel to a remote site, where they eventually convert back to their epithelial state and clump together into a secondary tumor.

Working with human breast tissue, the new study's authors attempted to induce EMT in normal cells; they figured they would just get fibroblasts, a type of connective tissue that is important in wound healing. When they looked closely, however, they noted that the transformed cells had surface proteins that were common to stem cells. Cultured in the lab, the changed cells showed an ability to differentiate into (or become) two discrete cells found in breast tissue. And the transformed cells proved to be very similar to actual stem cells from both mice and humans.

"What we're doing is inducing dedifferentiation," Mani says. He noted that it's not yet clear how far these cells can go down the path to immaturity—and, with it, the ability to become any tissue in the body. "We found, surprisingly, that EMT and stem cells could be linked; we show that, yes, they are very closely linked."

Mani says that the scientists may next pursue two paths: The team can determine how to stop cancer cells from undergoing this transformation in the first place. Second—a path they are already pursuing—they can gauge these transformed adult cells' worth as stem cell surrogates for regenerative medicine.

As far as the promise of regenerative therapies, the team will attempt to determine just how stem cell–like these cells are by inducing EMT in epithelial cells from the mammaries of mice to see if they can grow a breast in the lab. If they succeed, they can be reasonably confident that epithelial cells can be taken from a patient and used to regenerate damaged tissue in that same person.

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