Journal of Gastroenterology

, Volume 47, Issue 2, pp 97–106 | Cite as

The inflammatory network in the gastrointestinal tumor microenvironment: lessons from mouse models

Review

Abstract

Accumulating evidence has indicated that inflammatory responses are important for cancer development. Epidemiological studies have shown that regular use of non-steroidal anti-inflammatory drugs (NSAIDs) reduces the risk of colon cancer development. Subsequently, mouse genetic studies have shown that cyclooxygenase (COX)-2, one of the target molecules of NSAIDs, and its downstream product, prostaglandin E2 (PGE2), play an important role in gastrointestinal tumorigenesis. Bacterial infection stimulates the Toll-like receptor (TLR)/MyD88 pathway in tumor tissues, which leads to the induction of COX-2 in stromal cells, including macrophages. Induction of the COX-2/PGE2 pathway in tumor stroma is important for the development and maintenance of an inflammatory microenvironment in gastrointestinal tumors. In such a microenvironment, tumor-associated macrophages express proinflammatory cytokines, including tumor necrosis factor (TNF)-α and interleukin (IL)-6, and these cytokines, respectively, activate the nuclear factor (NF)-κB and Stat3 transcription factors in epithelial cells, as well as in stromal cells. Recent mouse studies have uncovered the role of such an inflammatory network in the promotion of gastrointestinal tumor development. Genetically engineered and chemically induced mouse tumor models which mimic sporadic or inflammation-associated tumorigenesis were used in these studies. In this review article, we focus on mouse genetic studies using these tumor models, which have contributed to the elucidation of the molecular mechanisms associated with the inflammatory network in gastrointestinal tumors, and we also discuss the role of each pathway in cancer development. The involvement of immune cells such as macrophages, mast cells, and regulatory T cells in tumor promotion is also discussed.

Keywords

Gastrointestinal cancer Inflammation COX-2 NF-κB Stat3 

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Copyright information

© Springer 2011

Authors and Affiliations

  1. 1.Division of Genetics, Cancer Research InstituteKanazawa UniversityKanazawaJapan

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