Two teams of researchers have detected cancer stem cells in tumors from patients with colon cancer. When transplanted into mice, the cancer stem cells were able to form tumors that resembled the originals in patients, while most tumor cells could not.

Colon cancer is the latest type of cancer linked to these rare cells, which were first found in acute myeloid leukemia in 1994 and more recently in breast and brain tumors. The findings appeared online in two studies in Nature November 19.

Some researchers believe cancer stem cells are the driving force behind many cancers and will be found in nearly all tumors as the technology for finding them improves. The new studies, from investigators in Canada and in Italy, support this view.

"Our findings say that colon tumors are initiated and driven by this rare fraction of cells," says Dr. John Dick of the University of Toronto, who led the Canadian team. He also led the team that discovered leukemia stem cells in 1994.

In the new study, he asked: Do all of the tumor cells in colon cancers have the same ability to initiate new tumors and sustain their growth? The answer turned out to be no - only a subset of the tumor cells that produce a surface protein called CD133 could initiate new tumors in mice.

The results suggest that colon cancer may be organized in the same hierarchical fashion as organs are, with stem cells giving rise to "progenitor" cells that give rise to more specialized cells, says Dr. Dick.

Like the normal stem cells that repopulate adult tissues, cancer stem cells may divide indefinitely while giving rise to the cell types of a tumor. For therapies to be effective, it thus appears likely that they will have to eradicate the cancer stem cells.

But these cells have developed ways to avoid being killed. For instance, the cells may enter a dormant phase as some leukemia cancer stem cells do, notes Dr. Dick.

The Italian team, led by Dr. Ruggero De Maria of the Istituto Superiore di Sanità in Rome, also used the protein CD133 as a marker for identifying potential cancer stem cells. About 2.5 percent of the colon tumor cells they tested were positive for CD133.

This protein appears to be present on many cancer stem cells, but not every cell that is positive for CD133 is a cancer stem cell. As a next step, the Italian researchers are testing additional markers that might lead them to individual cancer stem cells.

"We are also setting up a cancer stem cell bank from different tumors," says Dr. De Maria. "We hope that the availability of cultures of tumor-causing colon cancer cells may foster the development of more effective therapies."

The appearance of two independent studies with similar conclusions serves as "instant validation of the questions at hand," says Dr. Jeremy Rich of Duke University Medical Center, who was not involved in the research.

Last month, his team reported that cancer stem cells in the brains of patients with glioblastoma may be resistant to radiation. Some observations about the behavior of colon cancer stem cells appear strikingly similar to what has been seen in the brain, he notes.

"This really suggests that cancer biology is, at its core, more similar than dissimilar, and this has important implications for therapy," says Dr. Rich.

By Edward R. Winstead