Contribution of TLR signaling to the pathogenesis of colitis-associated cancer in inflammatory bowel disease

World J Gastroenterol. 2014 Sep 28;20(36):12713-21. doi: 10.3748/wjg.v20.i36.12713.

Abstract

In the intestine a balance between proinflammatory and repair signals of the immune system is essential for the maintenance of intestinal homeostasis. The innate immunity ensures a primary host response to microbial invasion, which induces an inflammatory process to localize the infection and prevent systemic dissemination of pathogens. The key elements of this process are the germline encoded pattern recognition receptors including Toll-like receptors (TLRs). If pathogens cannot be eliminated, they may elicit chronic inflammation, which may be partly mediated via TLRs. Additionally, chronic inflammation has long been suggested to trigger tissue tumorous transformation. Inflammation, the seventh hallmark of cancer, may affect all phases of tumor development, and evade the immune system. Inflammation acts as a cellular stressor and may trigger DNA damage or genetic instability. Furthermore, chronic inflammation can provoke genetic mutations and epigenetic mechanisms that promote malignant cell transformation. Colorectal cancers in inflammatory bowel disease patients are considered typical examples of inflammation-related cancers. Although data regarding the role of TLRs in the pathomechanism of cancer-associated colitis are rather conflicting, functionally these molecules can be classified as "largely antitumorigenic" and "largely pro-tumorigenic" with the caveat that the underlying signaling pathways are mainly context (i.e., organ-, tissue-, cell-) and ligand-dependent.

Keywords: Carcinogenesis; Colitis-associated cancer; Immunoregulation; Inflammation; Inflammatory bowel disease; Tissue repair; Toll-like receptor.

Publication types

  • Editorial
  • Review

MeSH terms

  • Animals
  • Cell Transformation, Neoplastic / immunology
  • Cell Transformation, Neoplastic / metabolism*
  • Cell Transformation, Neoplastic / pathology
  • Colitis / complications*
  • Colitis / immunology
  • Colitis / metabolism
  • Colitis / pathology
  • Colon / immunology
  • Colon / metabolism*
  • Colon / pathology
  • Colonic Neoplasms / etiology*
  • Colonic Neoplasms / immunology
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology
  • Humans
  • Immunity, Innate
  • Inflammation Mediators / metabolism
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Signal Transduction*
  • Toll-Like Receptors / metabolism*

Substances

  • Inflammation Mediators
  • Toll-Like Receptors