Differential Expression of Aquaporin-3 and Aquaporin-5 in Pancreatic Ductal Adenocarcinoma

Direito, I; Paulino, J; Vigia, E; Brito, MA; Soveral, G

http://hdl.handle.net/10400.17/3834

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Abstract(s)

Background and objectives: Aquaporin-5 (AQP5) and -3 (AQP3) are protein channels that showed to be up-regulated in a variety of tumors. Our goal was to investigate the expression pattern of AQP5 and AQP3 in pancreatic ductal adenocarcinomas (PDA) and correlate with cell proliferation, tumor stage and progression, and clinical significance. Methods: 35 PDA samples in different stages of differentiation and locations were analyzed by immunohistochemistry for expression of AQP5, AQP3 and several markers of cell proliferation and tumorigenesis. Results: In PDA samples AQP5 was overexpressed in the apical membrane of intercalated and intralobular ductal cells while AQP3 was expressed at the plasma membrane of ductal cells. AQP5 was also found in infiltrative cancer cells in duodenum. Simultaneous overexpression of EGFR, Ki-67, and CK7, with decreased E-cad and increased Vim that characterize epithelial mesenchymal transition, tumor formation and invasion, strongly suggest AQP3 and AQP5 involvement in cell proliferation and transformation. AQP3 overexpression is reinforced in late and more aggressive PDA stages whereas AQP5 is related with tumor differentiation, suggesting it may represent a novel marker for PDA aggressiveness and intestinal infiltration. Conclusions: These findings suggest AQP3 and AQP5 involvement in PDA development and the usefulness of AQP5 in early PDA diagnosis.

Keywords

CHLC CHBPT Adult Aged Female Adenocarcinoma / metabolism Humans Male Middle Aged Aquaporin 3 / metabolism Aquaporin 5 / metabolism Cadherins / metabolism Case-Control Studies ErbB Receptors / metabolism Keratins / metabolism Ki-67 Antigen / metabolism Neoplasm Proteins / metabolism Pancreatic Ducts / metabolism Pancreatic Neoplasms / metabolism