Molecular Link Mechanisms between Inflammation and Cancer
D. B. Vendramini-Costa and J. E. Carvalho
Affiliation: Pharmacology and Toxicology Division, Chemical, Biological and Agricultural Pluridisciplinary Research Center, Campinas State University, Campinas-SP, Brazil. PO Box: 6171.
Keywords: Cancer, inflammation, tumor microenvironment, carcinogenesis, eicosanoids, kinins, cytokines, chemokines, transcription factors, non-steroidal anti-inflammatory drugs (NSAIDs).
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.
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