Hypoxia promotes an inflammatory phenotype of fibroblasts in pancreatic cancer

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...

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Autores principales: Mello, Ashley M., Ngodup, Tenzin, Lee, Yusoo, Donahue, Katelyn L., Li, Jinju, Rao, Arvind, Carpenter, Eileen S., Crawford, Howard C., Pasca di Magliano, Marina, Lee, Kyoung Eun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Brief Communication
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9478137/
https://www.ncbi.nlm.nih.gov/pubmed/36109493
http://dx.doi.org/10.1038/s41389-022-00434-2
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author Mello, Ashley M.
Ngodup, Tenzin
Lee, Yusoo
Donahue, Katelyn L.
Li, Jinju
Rao, Arvind
Carpenter, Eileen S.
Crawford, Howard C.
Pasca di Magliano, Marina
Lee, Kyoung Eun
author_facet Mello, Ashley M.
Ngodup, Tenzin
Lee, Yusoo
Donahue, Katelyn L.
Li, Jinju
Rao, Arvind
Carpenter, Eileen S.
Crawford, Howard C.
Pasca di Magliano, Marina
Lee, Kyoung Eun
author_sort Mello, Ashley M.
collection PubMed
description 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.
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spelling pubmed-94781372022-09-17 Hypoxia promotes an inflammatory phenotype of fibroblasts in pancreatic cancer Mello, Ashley M. Ngodup, Tenzin Lee, Yusoo Donahue, Katelyn L. Li, Jinju Rao, Arvind Carpenter, Eileen S. Crawford, Howard C. Pasca di Magliano, Marina Lee, Kyoung Eun Oncogenesis Brief Communication 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. Nature Publishing Group UK 2022-09-15 /pmc/articles/PMC9478137/ /pubmed/36109493 http://dx.doi.org/10.1038/s41389-022-00434-2 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Brief Communication
Mello, Ashley M.
Ngodup, Tenzin
Lee, Yusoo
Donahue, Katelyn L.
Li, Jinju
Rao, Arvind
Carpenter, Eileen S.
Crawford, Howard C.
Pasca di Magliano, Marina
Lee, Kyoung Eun
Hypoxia promotes an inflammatory phenotype of fibroblasts in pancreatic cancer
title Hypoxia promotes an inflammatory phenotype of fibroblasts in pancreatic cancer
title_full Hypoxia promotes an inflammatory phenotype of fibroblasts in pancreatic cancer
title_fullStr Hypoxia promotes an inflammatory phenotype of fibroblasts in pancreatic cancer
title_full_unstemmed Hypoxia promotes an inflammatory phenotype of fibroblasts in pancreatic cancer
title_short Hypoxia promotes an inflammatory phenotype of fibroblasts in pancreatic cancer
title_sort hypoxia promotes an inflammatory phenotype of fibroblasts in pancreatic cancer
topic Brief Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9478137/
https://www.ncbi.nlm.nih.gov/pubmed/36109493
http://dx.doi.org/10.1038/s41389-022-00434-2
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