South African Journal of Science
On-line version ISSN 1996-7489
Chronic inflammation of both infective and non-infective origin has been implicated in the aetiology of approximately 30% of all human epithelial malignancies. The primary carcinogens are reactive oxygen species (ROS) derived from activated, infiltrating cells of the innate immune system, especially neutrophils, which inflict oxidative damage on the DNA of bystander epithelial cells. The consequence is gene modifications which initiate cellular transformation. The process of tumourigenesis is exacerbated by the sustained generation of pro-proliferative ROS, as well as by the release of neutrophil-derived cytokines and proteases, all of which contribute to tumour promotion and progression. It is now well recognised that, in addition to inflammation causing cancer, many cancers per se induce an inflammatory response, with a high magnitude of neutrophil influx being indicative of a poor prognosis. In this setting, CXC chemokines produced by tumours not only promote neutrophil influx and hyperreactivity, but also cause autocrine activation of the proliferation of the chemokine-producing tumour cells. These various mechanisms of inflammation-mediated tumourigenesis are the primary focus of this review, together with a consideration of neutrophil-targeted anti-inflammatory strategies with potential as adjunctive cancer therapy.
Keywords : angiogenesis; chemokines; cytokines; hydrogen peroxide; proteinases; redox signalling; reactive oxygen species.