| Literature DB >> 24823639 |
Florencia McAllister1, Jennifer M Bailey2, Janivette Alsina2, Christopher J Nirschl3, Rajni Sharma4, Hongni Fan3, Yanique Rattigan4, Jeffrey C Roeser2, Rachana H Lankapalli3, Hao Zhang5, Elizabeth M Jaffee3, Charles G Drake3, Franck Housseau3, Anirban Maitra6, Jay K Kolls7, Cynthia L Sears3, Drew M Pardoll3, Steven D Leach8.
Abstract
Many human cancers are dramatically accelerated by chronic inflammation. However, the specific cellular and molecular elements mediating this effect remain largely unknown. Using a murine model of pancreatic intraepithelial neoplasia (PanIN), we found that Kras(G12D) induces expression of functional IL-17 receptors on PanIN epithelial cells and also stimulates infiltration of the pancreatic stroma by IL-17-producing immune cells. Both effects are augmented by associated chronic pancreatitis, resulting in functional in vivo changes in PanIN epithelial gene expression. Forced IL-17 overexpression dramatically accelerates PanIN initiation and progression, while inhibition of IL-17 signaling using genetic or pharmacologic techniques effectively prevents PanIN formation. Together, these studies suggest that a hematopoietic-to-epithelial IL-17 signaling axis is a potent and requisite driver of PanIN formation.Entities:
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Year: 2014 PMID： 24823639 PMCID： PMC4072043 DOI： 10.1016/j.ccr.2014.03.014
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743