Year: 2022
Type: article
Abstract: Pancreatic ductal adenocarcinoma (PDAC) is characterized by an extensive fibroinflammatory stroma and often experiences conditions of insufficient oxygen availability or hypoxia. Cancer-associated fibroblasts (CAF) are a predominant and heterogeneous population of stromal cells within the pancreatic tumor microenvironment. Here, we uncover a previously unrecognized role for hypoxia in driving an inflammatory phenotype in PDAC CAFs. We identify hypoxia as a strong inducer of tumor IL1ɑ expression, which is required for inflammatory CAF (iCAF) formation. Notably, iCAFs preferentially reside in hypoxic regions of PDAC. Our data implicate hypoxia as a critical regulator of CAF heterogeneity in PDAC.
Source: Oncogenesis
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,790
Funders: U.S. Department of Defense, U.S. Department of Health and Human Services, American Cancer Society, U.S. Department of Veterans Affairs, Conquer Cancer Foundation, Concern Foundation, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, University of Michigan, American College of Gastroenterology, Swim Across America, National Institutes of Health, Medical School, University of Michigan, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, DOD Peer Reviewed Cancer Research Program
Awards: Research Training in Experimental Immunology, G109073144, G1280483932, G130714073, Interrupting Cellular Crosstalk in the Immunosuppressive Microenvironment of Pancreas Cancer, G135683362, G1404790370, G1686049839, G2051468510, G2112105340, Mechanisms of Pancreatic Inflammation, Tissue Repair and Carcinogenesis, G2698315143, G3418398990, Cancer Biology Training Program, B CELLS IN PANCREATIC TUMORIGENESIS, G4119534169, G4500581767, G463003637, G4700882120, G4902317799, G5181971854, G5204826640, G5258831990, Synthesizing Image-derived Heterogeneity with Genomic measurements for Assessing Disease Aggressiveness in Lower Grade Gliomas, G5850682332, Development of a Standardized Electronic Treatment Plan Builds for NCI-supported Clinical Trials Year 2, Metaplastic Tuft Cells in Pancreatic Cancer, Dosage-Dependent Hedgehog Signaling in Pancreatic Cancer, G6872968899, G7201975796, G7448966117, G9000056385, G9000058822, Interdepartmental Training in Pharmacological Sciences, G91032517
OpenAlex ID: W4295931452