The platelet NLRP3 inflammasome is upregulated in a murine model of pancreatic cancer and promotes platelet aggregation and tumor growth

Brian A. Boone, Pranav Murthy, Jennifer L. Miller-Ocuin, Xiaoyan Liang, Kira L. Russell, Patricia Loughran, Meinrad Gawaz, Michael T. Lotze, Herbert J. Zeh, Sebastian Vogel

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1603-1610
Number of pages8
JournalAnnals of Hematology
Volume98
Issue number7
DOIs
StatePublished - Jul 1 2019

Keywords

  • NLRP3 inflammasome
  • Pancreatic cancer
  • Platelet aggregation
  • Platelets

ASJC Scopus subject areas

  • Hematology

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