Wednesday, October 08, 2008

Attacking Cancer Stem Cells

A screening approach identifies drugs that halt cells that feed tumors.

By Courtney Humphries

Capturing cancer stem cells: A new method allows scientists to grow leukemic stem cells from mice (in red) outside the body when supporting cells from the bone marrow (green) are present. The method makes it possible to perform high-throughput screening for drugs that target cancer stem cells. Credit: Kimberly Hartwell

All cancer cells were once thought to be equal, but recent research suggests otherwise. A growing body of evidence indicates that only certain cancer cells are capable of generating and maintaining a tumor. Dubbed cancer stem cells, they can divide indefinitely to perpetuate the cancer over time. They may also be the reason why some therapies fail to wipe out a cancer entirely: cancer stem cells seem to be particularly resistant to standard cancer treatments and can remain behind like the roots of a weed.

If this hypothesis holds true, cancer stem cells could be the most promising target for new therapies. A team of researchers at Harvard Medical School has now developed a new way to find drugs that selectively kill cancer stem cells or prevent them from dividing. The team is currently using the method to identify drug candidates for leukemia, a disease for which cancer stem cells have been well characterized. The researchers believe that the approach could eventually extend to other kinds of cancer.

David Scadden, cochair of the Harvard Stem Cell Institute and a collaborator on the project, says that typical high-throughput drug screens, which use cell lines grown in petri dishes, don't always yield good results because the cells are too removed from their natural context. With stem cells in particular, he says, "the microenvironment seems to be an important contributor for how the cells function." When grown in the lab, the cells can lose their "stemness," or ability to generate new cells. Instead, the Harvard drug-screening method uses cells taken directly from diseased animals.

To better mimic the natural environment of cancer stem cells, the team incorporated other cells that support them. "Cancer cells don't exist in isolation," says Kimberly Hartwell, a research fellow at Brigham and Women's Hospital, who helped lead the project. In tissues, she says, these cells "may hijack the support system--what we call the stromal cells." Stromal cells form connective tissue surrounding an organ; scientists believe that they help provide an environment where stem cells flourish.

To find treatments for leukemia, the team first isolated leukemic stem cells from the bone marrow of diseased mice, then added them to stromal cells from the bone marrow. These two cell types were placed in plates with tiny wells that can be treated with drugs and analyzed using robotic methods. By transplanting the leukemic stem cells into a healthy mouse, the scientists have confirmed that the cells retain their ability to form new cancerous cells for up to four weeks.