Newswise — Mad cow disease is caused by the accumulation of an abnormal protein, the prion, in the brain of an affected patient. Outside of the brain, very little is known about prions. Case Western Reserve University School of Medicine, researchers have, for the first time, identified the prion as a biomarker for pancreatic cancer. Pancreatic cancer is one of the most deadly cancers in humans; the five year survival rate is less than 10 percent.
Chaoyang Li, Ph.D., Wei Xin, M.D., and professor of pathology, Man-Sun Sy, Ph.D., discovered the mechanism by which prions causes tumors to grow more aggressively. They published these findings in the September issue of the Journal of Clinical Investigation. Unlike normal cells, in human pancreatic cancer cells the prion is incompletely processed and binds to a molecule inside the cell known as filamin A. Filamin A is an important regulator of the cell's skeleton and its signaling machineries. The binding of the incompletely processed prion to filamin A disrupts the cell's organization and signaling. As a result, the tumor cells grow more aggressively. On the other hand, when the prion level is reduced, the tumor cell loses its ability to grow in tissue culture and in animals. Most importantly, Dr. Li, et al. found that a subpopulation of patients had incompletely processed prion protein in their pancreatic cancer. This subgroup of patients had significantly shorter survival compared to patients whose tumors do not have prion.
According to Dr. Sy, "Currently there is no early diagnostic marker for pancreatic cancer. Detection of the incompletely processed prion may provide such a marker. Preventing the binding of prion to filamin A may open new avenues for therapeutic intervention of this deadly disease."
Next, Drs. Li and Sy will look to determine if this type of prion protein expression is seen in other types of cancer.
About Case Western Reserve University School of Medicine
Founded in 1843, Case Western Reserve University School of Medicine is the largest medical research institution in Ohio and is among the nation's top medical schools for research funding from the National Institutes of Health. The School of Medicine is recognized throughout the international medical community for outstanding achievements in teaching. The School's innovative and pioneering Western Reserve2 curriculum interweaves four themes--research and scholarship, clinical mastery, leadership, and civic professionalism--to prepare students for the practice of evidence-based medicine in the rapidly changing health care environment of the 21st century. Eleven Nobel Laureates have been affiliated with the school.
Annually, the School of Medicine trains more than 800 M.D. and M.D./Ph.D. students and ranks in the top 25 among U.S. research-oriented medical schools as designated by U.S. News & World Report "Guide to Graduate Education."
The School of Medicine's primary affiliate is University Hospitals Case Medical Center and is additionally affiliated with MetroHealth Medical Center, the Louis Stokes Cleveland Department of Veterans Affairs Medical Center, and the Cleveland Clinic, with which it established the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University in 2002. http://casemed.case.edu.
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Journal of Clinical Investigation (Sep-2009)