May 15, 2008
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
By Nikhil Swaminathan
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,
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.
http://www.sciam.
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StemCells subscribers may also be interested in these sites:
Children's Neurobiological Solutions
http://www.CNSfoundation.org/
Cord Blood Registry
http://www.CordBlood.com/at.cgi?a=150123
The CNS Healing Group
http://groups.yahoo.com/group/CNS_Healing
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