Researchers have detected cancer stem cells in tumors from patients with pancreatic cancer. Experiments in mice suggest that these cancer stem cells may help explain the aggressive growth and spread of pancreatic tumors seen in patients, the researchers report in the February 1 Cancer Research.

Cancer stem cells have been identified in blood, brain, and breast cancers, and more recently in ovarian and colon cancers. The new findings provide further support for the stem cell hypothesis, the theory that some tumors contain small populations of self-renewing cells that give rise to all of the cells in the tumor.

Though cancer stem cells make up less than 5 percent of a tumor, they may underlie the cancer and be resistant to conventional treatments.

"The new research adds to the growing evidence that within tumors there is a small subset of cells that drives the tumor and that has stem cell-like characteristics," says lead researcher Dr. Diane M. Simeone of the University of Michigan Medical Center.

A defining characteristic of human cancer stem cells is the ability to grow new tumors in mice. As few as 100 pancreatic cancer stem cells could regenerate copies of the original tumor when transplanted into mice, the researchers found. Some tumors rapidly spread to other organs, as often happens in patients.

The aggressive behavior of the cells in mice is consistent with what clinicians have observed in patients with the disease, the researchers say.

Pancreatic cancer is so deadly because it is often diagnosed late and because tumors are notoriously resistant to standard chemotherapy and radiation. The disease is the 4th deadliest cancer in the United States, even though it ranks 11th in incidence.

"Cancer stem cells represent a whole new way of thinking about the disease," says Dr. Simeone. Her team has preliminary evidence that pancreatic cancer stem cells may not be touched by conventional treatment, and they will be testing this in the coming months.

The new findings will influence research on pancreatic cancer almost immediately, predicts Dr. J. Milburn Jessup of NCI's Division of Cancer Treatment and Diagnosis.

"The study shows that it is possible to isolate the pancreatic cancer stem cell in order to investigate its properties, determine its weaknesses, and then develop therapies that target this cell," says Dr. Jessup.

Along with new therapies, new ways of evaluating these therapies may be needed. The current method of measuring tumor size would clearly be inadequate given the likelihood that a tumor would return despite shrinking.

"In the future we might need to measure the burden of cancer stem cells in tumors before and after therapies in order to establish their effectiveness," says Dr. Simeone.

Even though cancer stem cells appear to be relatively resistant to therapy, "these cells may prove to be the Achilles heel of the cancer," notes Dr. Jessup.

To identify potential pancreatic cancer stem cells, Dr. Simeone's team looked for tumor cells with three surface proteins that have been found to characterize breast cancer stem cells - CD44, CD24, and ESA. They are also testing other proteins used as potential markers for cancer stem cells.

Dr. Michael Clarke of Stanford University School of Medicine and Dr. Max Wicha, also at Michigan, led the team that identified the breast cancer stem cells in 2003. Both are co-authors of the new study.

By Edward R. Winstead