Disruption of retinol-mediated IL-6 expression in colon cancer-associated fibroblasts: new perspectives on the role of vitamin A metabolism

Romain Villéger; Marina Chulkina; Randy C. Mifflin; Don W. Powell; Irina V. Pinchuk

doi:10.18632/oncotarget.28399

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Research Perspectives:

Disruption of retinol-mediated IL-6 expression in colon cancer-associated fibroblasts: new perspectives on the role of vitamin A metabolism

Romain Villéger, Marina Chulkina, Randy C. Mifflin, Don W. Powell and Irina V. Pinchuk _

PDF | Full Text | How to cite | Press Release

Oncotarget. 2023; 14:377-381. https://doi.org/10.18632/oncotarget.28399

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Abstract

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

Correspondence to:

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

Copyright: © 2023 Villéger et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ABSTRACT

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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Research Perspectives:

Disruption of retinol-mediated IL-6 expression in colon cancer-associated fibroblasts: new perspectives on the role of vitamin A metabolism

Abstract