In a path-breaking discovery, researchers at the U-M Comprehensive Cancer Center and Stanford University School of Medicine have identified cancer stem cells that are responsible for triggering growth of head and neck tumors. The study is detailed in the Jan. 16 issue of the Proceedings of the National Academy of Sciences. 

Cancer stem cells are a small group of cells that are believed to be the driving force behind the replication of tumors. These cells multiply and then direct the growth of cancer. Researchers are of the opinion that the major cause of failure of many cancer treatments is the inability to target these stem cells or markers that are vital for cancer progression. The new finding holds hope that drugs may eventually be developed to target these cancer stem cells thus halting the growth of cancer.
Lead researcher Mark Prince, M.D., assistant professor of otolaryngology at the University of Michigan Medical School said as much, “Our treatment results for head and neck cancer are not as good as we’d like them to be. A lot of people still die of head and neck cancer. This finding will impact our understanding of head and neck cancer, and we hope it will lead to treatments that will be more effective,” he added.

Researchers at the U-M Comprehensive Cancer Center and Stanford University School of Medicine took tumor samples from patients undergoing surgery for head and neck squamous cell carcinoma, including cancers of the tongue, larynx, throat and sinus. Cells from the samples were separated based on whether they expressed a marker on their surface called CD44. The sorted cells were then implanted into immune-deficient mice to grow tumors.

The cells that expressed CD44 were able to grow new tumors, while the cells that did not express CD44 did not grow new tumors. The tumors that grew were found to be identical to the original tumors and to contain cells that expressed CD44 as well as cells that did not express the marker. This ability to both self-renew and produce different types of cells is a hallmark of stem cells.

Stem cells have been identified in several other cancer types, including breast, brain, central nervous system and colon cancers, as well as leukemia. U-M researchers in 2003 were the first to report the existence of stem cells in a solid tumor, finding them in breast cancer. CD44 was also found to play a role in breast cancer stem cells.

“We know CD44 is important in breast cancer and now in head and neck cancer, so it might be important in other cancer types. This work gives more evidence that the cancer stem cell theory is valid,” Prince says.

That theory suggests that a small subpopulation of cancer cells are the critical cells in cancer growth and progression, and the key to treating it is to kill the stem cells. It’s a radically different model than current treatment approaches, which are designed to shrink the tumor by killing as many cells as possible. Researchers suspect cancer recurs because the treatments are not killing the stem cells.

The current finding in head and neck tumors does not pinpoint the exact stem cells, the researchers believe, but rather narrows down the field. The percent of cells within a tumor expressing CD44 varied from one sample to the next, with one sample composed of as high as 40 percent of these cells. Studies in other cancer types have found the stem cell population to be smaller than 5 percent.

“The CD44-positive cells contain the tumorigenic cells, but we don’t think that’s a pure population of cancer stem cells. We still need to drill down further to find the subpopulation of those cells that is the pure version,” Prince says.

In addition to Prince, U-M study authors were doctoral student Andrew Kaczorowski and Gregory Wolf, M.D., professor and chair of otolaryngology. Stanford authors were Ranjiv Sivanandan, Michael Kaplan, M.D.; Piero Dalerba; Irving Weissman, M.D.; Michael Clarke, M.D.; and Laurie Ailles.

Funding for the study was from the U-M Specialized Program of Research Excellence ( SPORE ) grant in head and neck cancer and from an anonymous gift fund for cancer stem cell research at Stanford University.

While promising, this research is still in the early stages of animal testing, and more research must be done before it could benefit patients with head and neck cancer. No therapeutic treatments or clinical trials are available at this time. For information on existing options for head and neck cancer, call Cancer AnswerLine at 800-865-1125 or visit www.cancer.med.umich.edu/cancertreat/headandneck/index.shtml.

Reference: Proceedings of the NationalAcademy of Sciences, Vol. 104, No. 3, pp. 973-978