Pro-malignant properties of STAT3 during chronic inflammation.

Already in 1863 Rudolph Virchow hypothesized that some classes of irritants, together with tissue injury, enhance cell proliferation and that cancer arises from sites of chronic inflammation. Although now we know that cell proliferation is not a cause of cancer on itself, for the first time his hypothesis suggested a link between cell transformation and inflammation. Many tumors contain activated fibroblasts and macrophages displaying an inflammatory gene expression profile. Interestingly, quantitative aspects of wound repair or inflammatory gene expression often negatively correlate with cancer stage and prognosis: in a sense, tumors act as wounds that fail to heal [1]. Chronic inflammatory states may generate a microenvironment favoring genomic lesions and fostering tumor initiation. The presence of free radicals, such as reactive oxygen intermediates and nitric oxide, leads to oxidative damage and nitration of DNA bases, which in turn increases the risk of mutations. Moreover, the soluble mediators secreted by inflammatory cells such as cytokines and growth factors provide survival and proliferative signals to initiated cells, thereby leading to tumor promotion/progression.