Hypoxia promotes an inflammatory phenotype of fibroblasts in pancreatic cancer
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Sep 15, 2022
- Source ID
- 10.1038/s41389-022-00434-2
Entities
People
- Arvind Rao
- Ashley M. Mello
- Eileen S. Carpenter
- Howard C. Crawford
- Jinju Li
- Katelyn L. Donahue
- Kyoung Eun Lee
- Marina Pasca di Magliano
- Tenzin Ngodup
- Yusoo Lee
Organizations
- American Cancer Society
- American College of Gastroenterology
- Concern Foundation
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases
- National Cancer Institute
- National Institute of General Medical Sciences
- Swim Across America
- United States Department of Defense
- United States Department of Health and Human Services
- United States Department of Veterans Affairs