Molecular Link Mechanisms between Inflammation and Cancer

D.      B. Vendramini-Costa; J.      E. Carvalho

doi:10.2174/138161212802083707

Abstract

Inflammation is part of the body's response to internal and external environmental stimuli that normally eliminate the aggressor agent and restore the tissue physiology. However, when it becomes chronic, it can cause several pathologies such as cardiovascular, diabetes, rheumatoid arthritis, Alzheimer's autoimmune diseases and cancer. Currently, epidemiological data indicate that over 25% of all cancers are related to chronic infections and other types of unresolved inflammation. Further evidence of this relationship is the fact that prolonged use of non-steroidal anti-inflammatory drugs (NSAIDs) has been associated with reduced risk to developing many types of cancers. Some randomized trials have shown that NSAIDs have protective action against colon adenomas, breast, prostate, and lung cancers. The inflammation present on tumor microenvironment is characterized by leukocyte infiltration, ranging in size, distribution and composition, as: tumor-associated macrophages (TAM), mast cells, dendritic cells, natural killer (NK) cells, neutrophils, eosinophils and lymphocytes. These cells produce a variety of cytotoxic mediators such as reactive oxygen and nitrogen species (ROS and RNS respectively), serine and cysteine proteases, membrane perforating agents, matrix metalloproteinase (MMP), tumor necrosis factor α (TNFα), interleukins (IL-1, IL-6, IL-8), interferons (IFNs) and enzymes, as cyclooxygenase-2 (COX-2), lipooxygenase-5 (LOX-5) and phospholipase A2 (PLA2), which activate or are activated by transcription factors as nuclear factor κB (NF-κB) and signal transducers and activators of transcription-3 (STAT3). Initially this paper will briefly review the main mediators present on tumor microenvironment, addressing the cytokines, chemokines, transcription factors, eicosanoid, and kinins and later, will present an overview of the role of inflammation in the different steps of carcinogenesis.

Keywords: Cancer, inflammation, tumor microenvironment, carcinogenesis, eicosanoids, kinins, cytokines, chemokines, transcription factors, non-steroidal anti-inflammatory drugs (NSAIDs).