1. Oncogenic Kras Activates a Hematopoietic-to-Epithelial IL-17 Signaling Axis in Preinvasive Pancreatic Neoplasia.
- Author
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McAllister, Florencia, Bailey, Jennifer?M., Alsina, Janivette, Nirschl, Christopher?J., Sharma, Rajni, Fan, Hongni, Rattigan, Yanique, Roeser, Jeffrey?C., Lankapalli, Rachana?H., Zhang, Hao, Jaffee, Elizabeth?M., Drake, Charles?G., Housseau, Franck, Maitra, Anirban, Kolls, Jay?K., Sears, Cynthia?L., Pardoll, Drew?M., and Leach, Steven?D.
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PANCREATIC cancer , *CELLULAR signal transduction , *INTERLEUKIN-17 , *HEMATOPOIETIC stem cells , *CANCER invasiveness , *GUANOSINE triphosphatase - Abstract
Summary: 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 KrasG12D 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. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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