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Archives of Toxicology

, Volume 90, Issue 9, pp 2109–2130 | Cite as

RETRACTED ARTICLE: Mouse models of intestinal inflammation and cancer

  • Aya M. Westbrook
  • Akos Szakmary
  • Robert H. Schiestl
Review Article

Abstract

Chronic inflammation is strongly associated with approximately one-fifth of all human cancers. Arising from combinations of factors such as environmental exposures, diet, inherited gene polymorphisms, infections, or from dysfunctions of the immune response, chronic inflammation begins as an attempt of the body to remove injurious stimuli; however, over time, this results in continuous tissue destruction and promotion and maintenance of carcinogenesis. Here, we focus on intestinal inflammation and its associated cancers, a group of diseases on the rise and affecting millions of people worldwide. Intestinal inflammation can be widely grouped into inflammatory bowel diseases (ulcerative colitis and Crohn’s disease) and celiac disease. Long-standing intestinal inflammation is associated with colorectal cancer and small-bowel adenocarcinoma, as well as extraintestinal manifestations, including lymphomas and autoimmune diseases. This article highlights potential mechanisms of pathogenesis in inflammatory bowel diseases and celiac disease, as well as those involved in the progression to associated cancers, most of which have been identified from studies utilizing mouse models of intestinal inflammation. Mouse models of intestinal inflammation can be widely grouped into chemically induced models; genetic models, which make up the bulk of the studied models; adoptive transfer models; and spontaneous models. Studies in these models have lead to the understanding that persistent antigen exposure in the intestinal lumen, in combination with loss of epithelial barrier function, and dysfunction and dysregulation of the innate and adaptive immune responses lead to chronic intestinal inflammation. Transcriptional changes in this environment leading to cell survival, hyperplasia, promotion of angiogenesis, persistent DNA damage, or insufficient repair of DNA damage due to an excess of proinflammatory mediators are then thought to lead to sustained malignant transformation. With regard to extraintestinal manifestations such as lymphoma, however, more suitable models are required to further investigate the complex and heterogeneous mechanisms that may be at play.

Keywords

Intestinal inflammation Intestinal cancer Mouse models 

Notes

Acknowledgments

This work was supported in part by NIH Grant ES09519 (RS), the Jonsson Comprehensive Cancer Foundation (RS), a TRP Grant (L618-B11) from the FWF (AS and RS) and a UCLA-NIEHS training grant in Molecular Toxicology (AW).

Compliance with ethical standards

Conflict of interest

The authors declare that there are no conflicts of interest.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Aya M. Westbrook
    • 1
    • 2
  • Akos Szakmary
    • 3
  • Robert H. Schiestl
    • 1
    • 2
  1. 1.Molecular Toxicology Interdepartmental Program, UCLA School of Medicine and School of Public HealthUniversity of California at Los AngelesLos AngelesUSA
  2. 2.Department of Pathology and Lab Medicine, UCLA School of Medicine and School of Public HealthUniversity of California at Los AngelesLos AngelesUSA
  3. 3.Institute for Cancer ResearchMedical University of ViennaViennaAustria

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