Disruption of retinol-mediated IL-6 expression in colon cancer-associated fibroblasts: new perspectives on the role of vitamin A metabolism
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Romain Villéger1, Marina Chulkina2, Randy C. Mifflin3, Don W. Powell3,4,5 and Irina V. Pinchuk2
1 Université de Poitiers, UMR CNRS 7267, Ecologie et Biologie des Interactions, France
2 Department of Medicine at Penn State Health Milton S. Hershey Medical Center, Hershey, PA 17033, USA
3 Department of Internal Medicine, Division of Gastroenterology and Hepatology, UTMB, Galveston, TX 77555, USA
4 Institute for Translational Sciences, UTMB, Galveston, TX 77555, USA
5 Department of Neuroscience and Cell Biology, UTMB, Galveston, TX 77555, USA
|Iryna V. Pinchuk,||email:||[email protected]|
Keywords: tumor microenvironment; colon cancer; inflammation; fibroblasts; IL-6
Received: February 28, 2023 Accepted: March 22, 2023 Published: April 26, 2023
Stromal myo-/fibroblasts (MFs) account for up to 30% of lamina propria cells in the normal human colon and their number is dramatically increased in colon cancer (CRC). Fibroblasts from cancers, also known as cancer-associated fibroblasts (CAFs), differ from normal colonic MF (N-MFs) and support tumor-promoting inflammation, in part due to increased IL-6 secretion. In this research perspective, we highlight recent data obtained regarding IL-6 regulation in colorectal cancer CAFs through vitamin A (retinol) metabolism, discuss current limitations in our understanding of the mechanisms leading to the CAF pro-inflammatory phenotype, and discuss potential approaches to target CAF retinoid metabolism during CRC treatment.
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