Nuclear factor kappaB-activated monocytes contribute to pancreatic cancer progression through the production of Shh
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Recently, it was reported that Hh signaling is activated in tumor stromal cells but not in tumor cells themselves and that stromal cells may play a role in the proliferation of cancer cells. This suggests the possibility that stromal cells have an important role in the proliferation of tumor cells that may be mediated through Hh signaling. In this report, we present for the first time that inflammation-stimulated monocytes produce Shh through activation of the NF-κB signaling pathway, and that the Shh produced promotes the proliferation of pancreatic cancer cells in a paracrine manner through Hh signaling.
KeywordsNF-κB Hh pathway Monocytes Pancreatic cancer
Peripheral blood mononuclear cells
Pancreatic ductal adenocarcinomas
This study was supported by General Scientific Research Grants (21390363) from the Ministry of Education, Culture, Sports and Technology of Japan. We thank Dr. K. Takeda for kindly providing us with the NF-κB-dependent luciferase reporter, Dr. Aubie Shaw for kindly providing us with pSHH-GFP plasmids, and Dr. H. Yamamoto from Department of Anatomic Pathology, Kyushu University, for giving us an appropriate technical advice about immunohistochemistry. We also thank Kaori Nomiyama for the skillful technical assistance.
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