The platelet NLRP3 inflammasome is upregulated in a murine model of pancreatic cancer and promotes platelet aggregation and tumor growth
Autor: | Herbert J. Zeh, Meinrad Gawaz, Jennifer L. Miller-Ocuin, Michael T. Lotze, Xiaoyan Liang, Kira L. Russell, Pranav Murthy, Brian A. Boone, Sebastian Vogel, Patricia Loughran |
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Rok vydání: | 2019 |
Předmět: |
Blood Platelets
medicine.medical_specialty Platelet Aggregation Inflammasomes Article Mice 03 medical and health sciences 0302 clinical medicine Cell Line Tumor Internal medicine Pancreatic cancer NLR Family Pyrin Domain-Containing 3 Protein medicine Animals Platelet Platelet activation Mice Knockout Hematology integumentary system business.industry Inflammasome Neoplasms Experimental General Medicine medicine.disease Neoplasm Proteins Up-Regulation Gene Expression Regulation Neoplastic Pancreatic Neoplasms medicine.anatomical_structure Tumor progression 030220 oncology & carcinogenesis Cancer cell Cancer research business Pancreas 030215 immunology medicine.drug |
Zdroj: | Ann Hematol |
ISSN: | 1432-0584 0939-5555 |
Popis: | Platelets are activated in solid cancers, including pancreatic ductal adenocarcinoma (PDA), a highly aggressive malignancy with a devastating prognosis and limited therapeutic options. The mechanisms by which activated platelets regulate tumor progression are poorly understood. The nucleotide-binding domain leucine-rich repeat containing protein 3 (NLRP3) inflammasome is a key inflammatory mechanism recently identified in platelets, which controls platelet activation and aggregation. In an orthotopic PDA mouse model involving surgical implantation of Panc02 murine cancer cells into the tail of the pancreas, we show that the NLRP3 inflammasome in circulating platelets is upregulated in pancreatic cancer. Pharmacological inhibition or genetic ablation of NLRP3 in platelets resulted in decreased platelet activation, platelet aggregation, and tumor progression. Moreover, interfering with platelet NLRP3 signaling significantly improved survival of tumor-bearing mice. Hence, the platelet NLRP3 inflammasome plays a critical role in PDA and might represent a novel therapeutic target. |
Databáze: | OpenAIRE |
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