In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 76, No. 24_Supplement ( 2016-12-15), p. B69-B69
Abstract:
The tuft cell is a chemosensory cell type that can interpret signals from luminal surfaces throughout the body in order to activate downstream effectors. One clear effector pathway of the tuft cell promotes a type-two immune response in the intestine after parasitic infection, suggesting that this cell population has the ability to communicate with the immune system. Furthermore, tuft cells have also been shown to activate sensory nerve fibers to lead to the production of a neuroinflammatory signal in the nasal epithelium. Therefore, tuft cells can promote effector inflammatory responses through direct immune cell signaling and through sensory nerve fibers. Pancreatic ductal adenocarcinoma (PDA) is characterized by a robust stromal reaction, a large component of which is composed of an immune response. It has been previously studied that this inflammatory response can function to promote both the initiation and progression of PDA. One mechanism by which inflammatory cells can be recruited to the pancreas is through neuroinflammatory pathways. Work with collaborators has shown that pancreatic sensory neurons are required for the progression of PDA, as ablation of this cell type significantly prolongs survival. Interestingly, tuft cells in the metaplastic pancreas have been shown to appear during transdifferentiation and progression to PDA. These tuft cells also possess key signaling elements that have the potential to mediate the response to extracellular signals, such as α-gustducin and TRPM5. Metaplastic tuft cells also produce the proteins necessary to make or release prostaglandins, acetylcholine and ATP, all of which can stimulate either a direct immunomodulatory signal or activate sensory nerve fibers. This leads us to hypothesize that tuft cells are a key mediator of signals to the stromal immune compartment and to sensory neurons in order to promote a robust immune response. In order to answer this question we are using chemosensory knockout animals to ablate critical signaling components of the chemosensory cascade to study the progression of PDA. Citation Format: Megan T. Hoffman, Shan Gao, Howard Crawford.{Authors}. Tuft cell signaling can induce pancreatic inflammation and promote pancreatic ductal adenocarcinoma. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr B69.
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.PANCA16-B69
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2016
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
