Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer related deaths in the United States and one of the most lethal human cancers. Chronic pancreatitis, which is characterized by inflammation of the pancreas, is a well-known risk factor for PDAC in humans. However, the precise mechanisms whereby chronic pancreatitis promotes pancreatic tumorigenesis remain elusive. Hypoxia, a condition of insufficient oxygen availability, occurs in the context of pancreatic cancer as well as chronic pancreatitis, suggesting that hypoxia is a link between chronic inflammation of the pancreas and carcinogenesis. Hypoxia inducible factor 1α (HIF-1α) is a principal mediator of hypoxic responses. HIF-1α has also been shown to tightly regulate inflammatory responses of myeloid cells. To elucidate the effects of HIF-1α on chronic inflammatory injury and regeneration of the pancreas, and define the role of HIF-1α in pancreatic cancer development, we generated mice that spontaneously develop PDAC with HIF-1α ablated. Our results indicate that HIF-1α impacts both the resolution of pancreatitis as well as the progression of pancreatic neoplasia and inflammatory cell recruitment.

Citation Format: M. Celeste Simon. A hypoxic microenvironment influences pancreatic cancer progression. [abstract]. In: Abstracts: AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment; 2014 Feb 26-Mar 1; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(1 Suppl):Abstract nr IA13. doi:10.1158/1538-7445.CHTME14-IA13