Editorial
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World J Gastroenterol. Sep 28, 2014; 20(36): 12713-12721
Published online Sep 28, 2014. doi: 10.3748/wjg.v20.i36.12713
Contribution of TLR signaling to the pathogenesis of colitis-associated cancer in inflammatory bowel disease
Ferenc Sipos, István Fűri, Miklós Constantinovits, Zsolt Tulassay, Györgyi Műzes
Ferenc Sipos, István Fűri, Miklós Constantinovits, Györgyi Műzes, 2nd Department of Internal Medicine, Semmelweis University, 1088 Budapest, Hungary
Zsolt Tulassay, Molecular Medicine Research Unit, Hungarian Academy of Sciences, 1088 Budapest, Hungary
Author contributions: Sipos F, Fűri I, Constantinovits M and Műzes G contributed to the writing and editing of this paper; Tulassay Z revised the manuscript.
Correspondence to: Györgyi Műzes, MD, CSc, PhD, 2nd Department of Internal Medicine, Semmelweis University, Szentkirályi Street 46, 1088 Budapest, Hungary. muzes.gyorgyi@med.semmelweis-univ.hu
Telephone: +36-1-2660926 Fax: +36-1-2660816
Received: February 28, 2014
Revised: April 28, 2014
Accepted: May 23, 2014
Published online: September 28, 2014
Processing time: 215 Days and 18.9 Hours
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: Inflammation; Tissue repair; Immunoregulation; Colitis-associated cancer; Toll-like receptor; Inflammatory bowel disease; Carcinogenesis

Core tip: Colorectal cancers arising in inflammatory bowel disease patients are considered typical examples of inflammation-associated cancers. The exact role of Toll-like receptor (TLR)-signaling in colitis-associated cancer initiation and development is conflicting. Here we aimed to summarize recent data on the contribution of TLR-mediated immune responses to inflamation-related colonic carcinogenesis.