Utilization of Notch1 and Prion Markers to Detecting Pluripotent Pancreatic Cells: An Autopsy Study
H Hu, W Xin. University Hospital Case Medical Center, Cleveland, OH; Case Western Reserve University, Cleveland
Background: The normal form of cellular prior protein (PrP) is a GPI anchored membrane protein, and are expressed in many cell types. The over-expression of PrP has been identified in many tumor cells, including gastric, breast and pancreatic cancers. We also found that PrP expression in precursor cells in fetal pancreas but not in adult pancreas. These precursor cells have similar morphology to the centroacinar cells which can differentiate to endocrine cells, ductal cells and acinar cells. Multiple cell types of the pancreas appear asynchronously during embryogenesis, which requires that pancreatic progenitor cell potential changes over time. Notch signaling pathway plays an important role in the process of pancreatic embryogenesis. So it is interesting to know the developmental expression patterns of Notch1 and PrP in fetal and adult pancreas.
Design: Forty-three autopsy cases between years 2002-2009, from gestational age 14 weeks to 18 years after birth, were retrieved. Normal pancreatic tissue resected for non-pancreatic neoplasms in 20 patients, ranging from 25 to 77 years old, were obtained as well. Immunohistochemical study was performed using monoclonal antibodies specific for PrP, Notch1, AE1/AE3, and a panel of neuroendocrine markers.
Results: The expressions of PrP are identified in endocrine cells and centroacinar cells of the pancreas, from fetal to adult; while notch 1 expression identified in acinar cells and centroacinar cells. Neither PrP and Notch 1 expression are detected in developed ducts in any pancreas. Abundant centroacinar cells expressing both PrP and Notch 1, which carries both acinar and endocrine lineage markers, identified in pancreas from gestational age 14 weeks to 3 months after birth. After that period, the centroacinar cells expressing both PrP and Notch1 decreased dramatically.
Conclusions: In different developmental stages of pancreas, PrP expression present only in mature and precursor cells of neuroendocrine lineage; while notch 1 expression present in mature and precursor cells of acinar cells. In fetal and young pancreas, centroacinar cells have both PrP and Notch 1 expression. The data suggest that utilization of co-expression of PrP and Notch 1 could identified pluripotent cells in pancreas, which may shed light on pancreatic carcinoma stem cell and/or diabetes mellitus research.
Wednesday, March 24, 2010 9:30 AM
Poster Session V # 16, Wednesday Morning