Study expands understanding of the origins of cancer stem cells

Michael Cleary

Researchers may need to broaden their views about the origin of cancer stem cells and their presumed rarity. New evidence suggests that the cells may be much more common than previously thought and more diverse in where they originate.

"I think in five to 10 years we may well have a very different understanding of what cancer stem cells actually are, including the possibility that the nature of these cells may vary from tumor to tumor," said Tim Somervaille, MD, PhD, postdoctoral scholar. His work with pathology professor Michael Cleary, MD, was published in the Oct. 16 issue of Cancer Cell.

Cancer stem cells are believed to be the cells that continuously replenish cancer, like the spring at the source of a creek. Only the cancer stem cell can form new cancer cells or cause relapse after treatment. The regular cancer cells, which en masse cause damage by their sheer bulk, cannot form new cancer cells on their own. Because of the cancer stem cell's deadly properties, many investigators believe that novel cancer therapies should specifically target and eradicate those cells.

To target therapies to cancer stem cells, you first have to know what they look like. With that in mind, many researchers have been searching for them in a variety of tumors and learning which cell in a given tissue eventually gives rise to the cancer stem cell.

The idea had been that cancer stem cells would share many of the features of normal tissue-specific stem cells and that such cells are quite rare within the cancer. But recent work by Cleary and Somervaille suggests that the story is more complex.

They've found that the cancer stem cells for a certain type of acute myeloid leukemia are both much more frequent and have less in common with tissue-specific stem cells than previously thought. Instead, the leukemia stem cells in a mouse model of the disease share many properties with more mature blood cells.

This complex picture began to emerge in 2004. At that time, Catriona Jamieson, MD, PhD, then a postdoctoral scholar working with Irv Weissman, MD, director of the Stanford Institute for Stem Cell Biology and Regenerative Medicine, reported that, in acute myeloid transformation of chronic myeloid leukemia, a cell that was not the blood-forming stem cell appeared to be a leukemia stem cell. Somervaille's experimental work now bolsters Jamieson's finding in a different type of leukemia.

Together, the studies show that leukemia may not necessarily arise from a blood-forming stem cell gone awry, but rather from the acquisition of stem-like properties by more mature cells that normally are limited in their growth potential.

Somervaille is funded by a Clinical Research Fellowship from the Leukemia Research Fund in the United Kingdom. Funding also came from the Children's Health Initiative of the Packard Foundation and PHS grants.