Gene expression dynamics in fibroblasts during early-stage murine pancreatic carcinogenesis.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by aggressive growth and metastasis, partly driven by fibroblast-mediated stromal interactions. Using RNA sequencing of fibroblasts from early-stage KPC mouse models, we identified significant upregulation of genes involved in adipogenesis, fatty acid metabolism, and the ROS pathway. ANGPTL4, a key adipogenesis regulator, was highly expressed in fibroblasts and promoted pancreatic cancer cell proliferation and migration through paracrine signaling.

Distance-depending transcriptome changes of pancreatic stellate cells in paracrine pancreatic ductal adenocarcinoma co-culture models.

Pancreatic stellate cells (PSC) are one source of cancer-associated fibroblasts (CAF) and play, therefore, an essential role in pancreatic ductal adenocarcinoma (PDA). Paracrine signalling between PDA cells and CAF has been widely studied, yet external influences on paracrine crosstalk are poorly understood. This study aimed to gain a deeper insight into the communication of PSC and cancer cells under different co-culture conditions via analysis of PSC gene expression profiles.

Cancer-Associated Fibroblasts and Tumor Cells in Pancreatic Cancer Microenvironment and Metastasis: Paracrine Regulators, Reciprocation and Exosomes.

Pancreatic cancer is currently the fourth leading cause of cancer deaths in the United States, and the overall 5 year survival rate is still only around 10%. Pancreatic cancer exhibits a remarkable resistance to established therapeutic options such as chemotherapy and radiotherapy, in part due to the dense stromal tumor microenvironment, where cancer-associated fibroblasts are the major stromal cell type. Cancer-associated fibroblasts further play a key role in cancer progression, invasion, and metastasis.