Chloroquine reduces hypercoagulability in pancreatic cancer through inhibition of neutrophil extracellular traps.

ABSTRACT:

Background

The hypercoagulable state associated with pancreatic adenocarcinoma (PDA) results in increased risk of venous thromboembolism, leading to substantial morbidity and mortality. Recently, neutrophil extracellular traps (NETs), whereby activated neutrophils release their intracellular contents containing DNA, histones, tissue factor, high mobility group box 1 (HMGB1) and other components have been implicated in PDA and in cancer-associated thrombosis.

Methods

Utilizing an orthotopic murine PDA model in C57/Bl6 mice and patient correlative samples, we studied the role of NETs in PDA hypercoagulability and targeted this pathway through treatment with the NET inhibitor chloroquine. PAD4 and RAGE knockout mice, deficient in NET formation, were used to study the role of NE

SUBMITTER: Boone BA 

PROVIDER: S-EPMC6013899 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature