DNA released from neutrophil extracellular traps (NETs) activates pancreatic stellate cells and enhances pancreatic tumor growth.

ABSTRACT: Neutrophil extracellular trap (NET) formation results in the expulsion of granulocyte proteins and DNA into the extracellular space. This process is mediated by the enzyme peptidyl arginine deiminase 4 (PADI4) and translocation of elastase to the nucleus. NET formation, marked by increased levels of extracellular DNA, promotes pancreatic cancer proliferation and metastasis. Mice deficient in Padi4 demonstrate decreased pancreatic tumor growth, associated with a reduction in circulating extracellular DNA levels, diminished pancreatic stromal activation and improved survival in murine orthotopic pancreatic adenocarcinoma. Transplantation of Padi4^-/- bone marrow into genetically engineered mice with Kras driven pancreatic adenocarcinoma (Pdx1-Cre:Kras^G12D/+, KC mice) lim

SUBMITTER: Miller-Ocuin JL 

PROVIDER: S-EPMC6685506 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature