Downregulation of the CCK-B Receptor in Pancreatic Stellate Cells Blocks Molecular Proliferative Pathways and Increases Apoptosis to Decrease Pancreatic Cancer Growth In Vitro.

ABSTRACT: Pancreatic cancer is characterized by an extensive fibrotic stroma largely driven by activated pancreatic stellate cells (PSCs)/fibroblasts, which also function to support tumor growth and metastasis. Cholecystokinin-B receptors (CCK-BRs) are expressed on pancreatic stellate cells (PSCs) and have emerged as a key regulator of PSC activation and tumor-stromal interactions. We hypothesized that disrupting CCK-BR function shifts PSCs to a more quiescent phenotype and reduces their pro-fibrotic and tumor-supportive activity to decrease growth of pancreatic cancer. Murine PSCs were genetically engineered with CRISPR-Cas9 to knockout the CCK-BR. In a series of experiments, the role of the CCK-BR expression was evaluated on cell migration, proliferation, differentially expressed genes, mol

SUBMITTER: Ortega M 

PROVIDER: S-EPMC12691738 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature