Researchers at the University of Michigan Comprehensive Cancer Center have found a marker that can be used to identify stem cells in breast tumors, suggesting a potential simple test that could help determine the best treatment for breast cancer.
The finding also provides strong support for the hypothesis that a small number of cells, called cancer stem cells, are responsible for fueling a tumor's growth.
U-M researchers were the first to discover stem cells in a solid tumor, finding them first in breast cancer. Generally, stem cells make up fewer than 5 percent of all the cells in a tumor, but they may be the key cells in cancer progression. The process of looking at the cell surface to identify stem cells, however, is too complex to apply to patient care.
In the new study, published in the November issue of Cell Stem Cell, the researchers found that cells from normal and cancerous breast tissue that had high levels of the enzyme aldehyde dehydrogenase activity, or ALDH, acted like breast stem cells. Further, of 577 human breast cancer tissue samples studied, those that expressed the specific form ALDH1 had the worst outcomes, suggesting this easily detected marker could be used to assess prognosis.
“This study is a big step because it provides a marker that's easy to use in both normal and cancer cells. Clinical applications were really not possible with the previously described markers. The fact that ALDH1 was identified in stem/progenitor cells from both normal and cancer tissue lends support to the idea that those cells are the primary target of transformation to malignancy. We believe it is only a very small population of cells that really are capable of unlimited growth and therefore drive cancer recurrence and metastasis,” says senior study author Gabriela Dontu, M.D., Ph.D., research assistant professor of internal medicine at the U-M Medical School.
Researchers used a reagent called ALDEFLUOR to detect the ALDH activity in the cells. Cells with high levels of this enzyme become fluorescent and can be detected. Cells can then be sorted to pull out the stained cells.
When they did this, researchers found that the ALDEFLUOR-positive cells acted like stem cells, while the ALDEFLUOR-negative cells did not. Stem cells are defined by their ability to generate identical cells as well as to differentiate into other types of cells.
The study also tested whether the separated cells could produce a breast tumor. Tumors formed only from the ALDEFLUOR-positive cells, even when as few as 500 cells were used. On the other hand, 50,000 ALDEFLUOR-negative cells did not generate tumors.
In addition to identifying the stem cells, the researchers found ALDH1 can indicate how aggressive a tumor is. In tissue samples from 577 patients with breast cancer, those bearing ALDH1-positive tumors had lower overall survival and were 1.76 times more likely to develop metastases than patients with ALDH1-negative tumors. ALDH1 was expressed in 19 percent to 30 percent of the tumors.