Tuft Cell Regulation of miRNAs in Pancreatic Cancer
Final rept. 30 Sep 2012-29 Sep 2014
OKLAHOMA UNIV HEALTH SCIENCES CENTER OKLAHOMA CITY
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To better understand the role of tuft cells in the pancreas and to define their effects on the pancreatic body as well as the initiation of pancreatic cancer. Tuft cells are present in the hollow organs of the digestive and respiratory tracts. They are characterized by long and blunt microvilli with prominent rootlets and by a well-developed tubulovesicular system in the supranuclear cytoplasm. Recent reports suggest that tuft cells may act as mechanoreceptors and are involved in chemosensensing of the microenvironment. With the successful deletion of Dclk1 throughout the pancreatic ducts, we have characterized, which extends our understanding of the role tuft cells play within ducts and their broader effects on the overall pancreatic microenvironment. We observed that Dclk1 co-localized with other putative tuft cell markers including Cox1 and Cox2. Additionally, we also observed the presence of the tuft cells of wild type and Pdx-1-CreDclk1floxlflox mice, indicating that Dclk1 may not play a role in tuft cells at baseline. We performed additional experiments to demonstrate the role of Dclk1 in pancreatic inflammation leading to pancreatic neoplasia. Dclk1 played a vital role in governing and is essential for pancreatic inflammatory process and associated metaplastic progression following caerulein-induced acinar ductal metaplasia. These finding could very well provide the basis for the development of novel chemotherapeutic drugs targeting these specialized cells expressing Dclk1 for eradication of pancreatitis and pancreatic adenocarcinoma.
- Medicine and Medical Research