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.
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 three markers.
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 original tumor. 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.
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.
Nicole Fawcett | EurekAlert!
Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute
Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water
In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...
The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.
Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
02.12.2016 | Medical Engineering
02.12.2016 | Agricultural and Forestry Science
02.12.2016 | Physics and Astronomy