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Colitis and cancer: a tale of inflammatory cells and their cytokines
Ezra Burstein, Eric R. Fearon
Ezra Burstein, Eric R. Fearon
Published January 24, 2008
Citation Information: J Clin Invest. 2008;118(2):464-467. https://doi.org/10.1172/JCI34831.
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Commentary

Colitis and cancer: a tale of inflammatory cells and their cytokines

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Abstract

Chronic inflammatory disorders are often associated with an increased cancer risk. A particularly striking example of the chronic inflammation–cancer link is seen in inflammatory bowel disease, in which chronic colitis or persistent inflammation in the colon is associated with elevated risk of colorectal cancer. Animal models exploring the mechanisms by which inflammation increases the risk of colon cancer have shown that inflammatory cells, through the effects of the cytokines they produce, have a major role in promoting neoplastic transformation. In this issue of the JCI, Popivanova and colleagues demonstrate that TNF-α, through its effects on the immune system, plays a critical role in promoting neoplastic transformation in this setting (see the related article beginning on page 560). Importantly, the study also provides evidence that anti–TNF-α therapies, which are currently in clinical use, may interrupt the process.

Authors

Ezra Burstein , Eric R. Fearon

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Figure 1

Role of TNF-α in inflammation associated with colorectal carcinogenesis.

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Role of TNF-α in inflammation associated with colorectal carcinogenesis....
Injury to the intestinal epithelium can result in DNA damage and altered gene expression and function, the initial step required for neoplastic transformation. In addition, this is accompanied by activation of NF-κB within epithelial cells, which promotes prosurvival pathways that are required for the initial growth of the resulting neoplastic cells. NF-κB activation also promotes proinflammatory gene expression. TNF-α originating from the mucosa or possibly the epithelium itself, participates in orchestrating the activation of immune cells. Production of various proinflammatory factors by the activated immune system participates in the ensuing inflammatory response but additionally plays a role in tumor growth by providing trophic signals to the early neoplastic lesions. Loss of TNF-α signaling in immune cells, and not the mucosa, stops this cascade by aborting the mucosal inflammatory response, and this can be achieved by pharmacologic blockade of TNF-α with etanercept and possibly other agents (21).

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ISSN: 0021-9738 (print), 1558-8238 (online)

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