Pancreatic stellate cells activated by mutant KRAS-mediated PAI-1 upregulation foster pancreatic cancer progression via IL-8.

ABSTRACT: Background: The dense fibrotic stroma enveloping pancreatic tumors is a major cause of drug resistance. Pancreatic stellate cells (PSCs) in the stroma can be activated to induce intra-tumor fibrosis and worsen patient survival; however, the molecular basics for the regulation of PSC activation remains unclear. Methods: The in vitro coculture system was used to study cancer cell-PSC interactions. Atomic force microscopy was used to measure the stiffness of tumor tissues and coculture gels. Cytokine arrays, qPCR, and Western blotting were performed to identify the potential factors involved in PSC activation and to elucidate underlying pathways. Results: PSC activation characterized by α-SMA expression was associated with increased pancreatic tumor stiffness and p

SUBMITTER: Wang HC 

PROVIDER: S-EPMC6831292 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature