Inflammatory bowel disease and intestinal cancer: a paradigm of the Yin-Yang interplay between inflammation and cancer.
Colon cancer represents a paradigm for the connection between inflammation and cancer in terms of epidemiology and mechanistic studies in preclinical models. Key components of cancer promoting inflammation include master transcription factors (for example, nuclear factor kappaB, STAT3), proinflammatory cytokines (for example, tumor necrosis factor, interleukin-6 (IL-6)), cyclooxygenase-2 and selected chemokines (for example, CCL2). Of no less importance are mediators that keep inflammation in check, including IL-10, transforming growth factorbeta, toll-like receptor and the IL-1 receptor inhibitor TIR8/SIGIRR, and the chemokine decoy and scavenger receptor D6. Dissection of molecular pathways involved in colitis-associated cancer may offer opportunities for innovative therapeutic strategies.
Danese
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Inflammatory Bowel Disease Unit, Division of Gastroenterology, Milan, Italy. sdanese@hotmail.com
Mantovani
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D018932:Chemokine CCL2 / Q000502:physiology; D051546:Cyclooxygenase 2 / Q000502:physiology; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000150:complications*; D016753:Interleukin-10 / Q000502:physiology; D015850:Interleukin-6 / Q000502:physiology; D007414:Intestinal Neoplasms / Q000209:etiology* / Q000276:immunology; D016328:NF-kappa B / Q000502:physiology; D017472:Receptors, Interleukin-1 / Q000502:physiology; D051193:Toll-Like Receptors / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D016709:Yin-Yang
D018932:Chemokine CCL2; D051546:Cyclooxygenase 2; D016753:Interleukin-10; D015850:Interleukin-6; D016328:NF-kappa B; D017472:Receptors, Interleukin-1; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; C111835:CCL2 protein, human; C546891:SIGIRR protein, human; C496540:PTGS2 protein, human