Chronic stress promotes pancreatic ductal adenocarcinoma progression via complement C5a-recruited myeloid-derived suppressor cells.

ABSTRACT: Chronic stress is an established risk factor for pancreatic ductal adenocarcinoma (PDAC). Although the autonomic nervous system (ANS), a key component of the tumor microenvironment (TME), has been closely associated with PDAC pathogenesis and prognosis, the underlying mechanisms remain incompletely understood. This study reveals that chronic stress-induced sympathetic nervous system (SNS) activation upregulates the hepatic complement system, leading to the recruitment of myeloid-derived suppressor cells (MDSCs) that promotes tumor progression. Specifically, chronic stress-triggered neurotransmitter norepinephrine (NE) enters the liver via systemic circulation and binds to upregulated β1 adrenergic receptor (ADRB1) on hepatocytes, enhancing the expression of complement components C3, C5, an

SUBMITTER: Yang S 

PROVIDER: S-EPMC12717323 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature