Penn State College of Medicine researchers, in collaboration with colleagues at the University of Southern California, have taken an important step in understanding the role of cell mother in the development of liver cancer. With a unique approach includes the study of individual cells, the team led by C.
Using a liver -specific PTEN (phosphatase and angiotensin homologue deleted on chromosome 10) mouse model allows Rountree and her colleagues to study the microenvironment of the liver, without affecting the rest of the mouse.
"The blow-out mouse PTEN is a model of chronic injury of the liver that eventually leads to liver cancer. During chronic injury, the cells proliferate and mother of the liver, sometimes healthy liver, the cells of the liver stem are very rare "Rountree said.”We were looking for a principle that is driving stem the proliferation of cells liver during chronic liver injury.
"We started the investigation of liver stem cells in many different models of liver injury with the idea that may be able to help people with liver disease, but we found that some isolated cells were malignant neoplasms," Rountree said. "It was a surprise to us because there were no tumors in mice when the cells were isolated."
The liver is the only body organ that is able to regenerate completely. Liver cells, including hepatocytes and cholangiocytes can divide and replenish themselves. With chronic liver injury, including a virus or alcoholism, hepatocytes lose their ability to do more for themselves. In this environment, the proliferation of liver stem cells can make either type of cells. However, patients with chronic injury also develop liver cancer, opening the possibility that stem cells involved in tumor formation.
"There has been a surge of interest in understanding the role of specific stem cells in the development of liver cancer," said Rountree. "Not a cancer stem cell lurking out there that can be very bad. It has properties of stem cells and malignant, resistant to chemotherapy. These properties make it more difficult to treat these cancers.
"What I ended up doing was changing our understanding of liver stem cells and their role in cancer," said Rountree. "All the work done previously was looking at patients, animal models or cell lines after the tumor developed. What we did was to identify malignant stem cells before there is evidence that the primary tumor. This gave us a new perspective not only the potential of stem cells for therapy is, but also in terms of what is driving the formation of cancer. Imagine a cancer treatment before it is a primary malignant tumor. "
The researchers created ten cell lines to study a single cell isolation technique. The cells that produce a unique surface protein called CD133 were separated by placing them in a liquid medium and run through a flow cytometer. Once identified, a robot took single CD133 positive cells and placed in a drop in a well of a culture plate. Doing this hundreds of times, cell lines were established.
These individual cells, when increased to, had characteristics of stem cells with markers of hepatocytes and cholangiocytes. When these lines were injected into a mouse with a deficient immune system, tumors formed.
Rountree said there is interest in using these stem cells with malignant potential. "We can target these cells in patients with hepatitis B or C, either before or after forms of cancer?" Rountree said. "The biggest implication is very powerful. If you look at a patient with a chronic injury and find a way to specifically target cells with malignant potential, may be able to prevent liver cancer in the first place."
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