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Ann Arbor - University of Michigan Comprehensive Cancer Center researchers have discovered the
small number of cells in pancreatic cancer that are capable of
fueling the tumor's growth. The finding is the first
identification of cancer stem cells in pancreatic tumors.
Pancreatic tumor generated from cancer stem cells
Cancer stem cells are the small number of cancer cells that replicate to drive tumor growth. Researchers believe
current cancer treatments sometimes fail because they are not attacking the cancer stem cells. By identifying the
stem cells, researchers can then develop drugs to target and kill these cells.
This is particularly crucial for pancreatic cancer, which has the worst survival rate of any major cancer type.
Nearly everyone who develops pancreatic cancer dies from the disease.
"Over the last one to two decades we have not had a significant improvement in the long-term survival rates with
pancreatic cancer. I believe that if we can target cancer stem cells within pancreatic cancer we may have an avenue
to really make a breakthrough in therapy for this awful disease," says lead study author
Diane Simeone, M.D., director of the Gastrointestinal Oncology Program at the U-M Comprehensive Cancer Center.
Researchers looked at cell markers on the surface of tumor cells and identified a small number of cells that
quickly produced new tumors. The researchers suggest these cells are the pancreatic cancer stem cells. Results
of the study appear in the Feb. 1 issue of Cancer Research.
Tissue samples were taken from 10 patients with pancreatic cancer. The samples were divided and implanted into
mice to grow new tumors, allowing a larger sample to be studied. The researchers sorted the tumor cells based on
whether they expressed certain antibody markers on the cell surface, specifically CD44, CD24 and epithelial-specific
antigen, or ESA. These three markers were chosen as a starting point based on previous work in breast cancer
stem cells. The researchers found that only 0.2 percent to 0.8 percent of the pancreatic cells expressed all
Researchers then took the sorted cells and injected them into mice to see if new tumors formed. When 100 cells
that expressed CD44, CD24 and ESA were injected, six of the 12 mice developed tumors. No tumors developed from the
cells negative for all three markers until 10,000 cells were injected, at which point one mouse developed a tumor.
Further, tumors that developed from these negative cells were smaller and grew more slowly than tumors from the
CD44, CD24 and ESA positive cells. The tumors that developed from these sorted cells appeared similar to the
In addition, the positive cells were able to reproduce cells that expressed the three markers as well as cells
negative for those markers. This ability to self-renew and produce different cells is a hallmark of stem cells.
"The fact that we saw very consistent results in 10 different patients supports that these cells are important,"
says Simeone, associate professor of surgery and of molecular and integrative physiology at the
U-M Medical School.
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, CD24 and ESA were also found to play a role in breast cancer
stem cells. A study published in January 2007 by U-M and Stanford University researchers narrowed the field for head
and neck cancer stem cells, again finding that cells expressing CD44 were involved.
Dr. Simeone in the lab
Extracting stem cells
Pancreatic Stem Cells
Researchers suggest that a small subpopulation of cancer cells are the critical cells in cancer growth and
progression, and the key to treating cancer is to kill these 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 model may lead to treatments limited in their effectiveness, because we have not been targeting
the most important cells in the tumor - the cancer stem cells. If we hope to cure more cancers we will need to
target and eliminate this critical type of cancer cell," says study author
Max S. Wicha, M.D., Distinguished Professor of Oncology and director of the U-M Comprehensive Cancer Center.
"With this finding in pancreatic cancer, we can now define what we believe are the important cells - the cells
that determine whether the cancer will come back or be cured - and target treatment directly to those cells," says
Wicha, who was part of the team that discovered stem cells in breast cancer.
About 33,700 people will be diagnosed with pancreatic cancer this year, and about 32,300 will die from it.
Five year survival rates are a dismal 3 percent. The disease is difficult to detect early and is often diagnosed
at advanced stages. Only 10 percent to 15 percent of patients can benefit from surgery.
"Stem cells are going to radically change how we treat cancer," Simeone says.
In addition to Simeone and Wicha, U-M study authors were research associate Chenwei Li; surgery resident David G.
Heidt, M.D.; Charles F. Burant, M.D., Ph.D., professor of molecular and integrative physiology and of internal
medicine; and research associate Lanjing Zhang. Other authors were Piero Dalerba and Volkan Adsay, M.D., from
Karmanos Cancer Institute in Detroit, and Michael F. Clarke, M.D., from Stanford University School of Medicine.
Funding for the study was from the Lustgarten Foundation, the Elsa Pardee Foundation, the Michigan Life Sciences
Corridor and the American Diabetes Association.
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 pancreatic cancer. No therapeutic treatments or clinical trials involving this
work are available at this time. For information on existing options for pancreatic cancer, call Cancer AnswerLine™
at 800-865-1125 or visit the pancreatic cancer web page.
The University of Michigan has filed for patent protection on the relevant technologies. In the event that
products come to market, the university and the inventors of these technologies will likely benefit financially.
For information about the process by which technologies make their way to market, and the rules that govern the
process, go to www.techtransfer.umich.edu.
Reference: Cancer Research, Vol. 67, No. 3
Written by Nicole Fawcett
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