Hypoxia promotes an inflammatory phenotype of fibroblasts in pancreatic cancer

Mello, A.; Ngodup, T.; Lee, Y.; Donahue, K. L.; Li, J.; Rao, A.; Carpenter, E. S.; Crawford, H. C.; Pasca di Magliano, M.; Lee, K. E.

doi:10.1101/2022.05.05.490771

bioRxiv · 10.1101/2022.05.05.490771

Hypoxia promotes an inflammatory phenotype of fibroblasts in pancreatic cancer

Mello, A.·Ngodup, T.·Lee, Y.·Donahue, K. L.·Li, J.·Rao, A.·Carpenter, E. S.·Crawford, H. C.·Pasca di Magliano, M.·Lee, K. E.

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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 IL1 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.

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Mello, A., Ngodup, T., Lee, Y., Donahue, K. L., Li, J., Rao, A., Carpenter, E. S., Crawford, H. C., Pasca di Magliano, M., Lee, K. E.. 2022-05-05. Hypoxia promotes an inflammatory phenotype of fibroblasts in pancreatic cancer. https://doi.org/10.1101/2022.05.05.490771

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