Thursday, August 20, 2009
THURSDAY, Aug. 20 (HealthDay News) -- A form of prion protein (PrP) may play a role in the aggressiveness of human pancreatic ductal adenocarcinoma (PDAC), according to research published Aug. 17 in the Journal of Clinical Investigation.
Chaoyang Li, Ph.D., of the Case Western Reserve University in Cleveland, and colleagues found that seven human PDAC cell lines expressed PrP. However, the PrP existed as a pro-protein that wasn't glycosylated or glycosylphosphatidylinositol (GPI)-anchored. The level of PrP varied among the lines, and was found both on the cell surface and in the cytoplasm.
The researchers found that binding of pro-prion protein (pro-PrP) to the filamin A (FLNa) cytolinker protein resulted in disruption of the cytoskeleton and signaling events in the PDAC lines. Inhibiting PrP expression in the cells reduced cellular proliferation and invasiveness. In addition, in patients treated surgically for pancreatic cancer, PrP expression in tumors was associated with shorter survival.
"Instead of being a GPI-anchored glycoprotein, PrP in human PDAC exists as pro-PrP, which binds to FLNa. This fatal attraction disrupts the normal functions of FLNa and confers a growth advantage to PDAC," the authors write. "Currently, there is no marker for early diagnosis of human PDAC; detection of pro-PrP could offer such a marker. Furthermore, prevention of the interaction between pro-PrP and FLNa could provide a novel target for therapeutic intervention in PDAC."
Diabetes & Endocrinology
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