Pharmacology and Toxicology Division, Chemical, Biological and Agricultural Pluridisciplinary Research Center, Campinas State University, Campinas-SP, Brazil.
Curr Pharm Des. 2012;18(26):3831-52. doi: 10.2174/138161212802083707.
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.
炎症是机体对外界环境刺激的一种反应，通常能消除侵害物并恢复组织生理学功能。然而，当炎症转为慢性时，可能会引发多种病理，如心血管疾病、糖尿病、类风湿性关节炎、阿尔茨海默氏病、自身免疫性疾病和癌症等。目前，流行病学数据表明，超过 25%的癌症与慢性感染和其他类型的未解决炎症有关。这种关系的进一步证据是，长期使用非甾体抗炎药（NSAIDs）与降低多种癌症的发病风险有关。一些随机试验表明，NSAIDs 对结肠癌腺瘤、乳腺癌、前列腺癌和肺癌具有保护作用。肿瘤微环境中的炎症表现为白细胞浸润，其大小、分布和组成各不相同，主要包括肿瘤相关巨噬细胞（TAM）、肥大细胞、树突状细胞、自然杀伤（NK）细胞、中性粒细胞、嗜酸性粒细胞和淋巴细胞等。这些细胞会产生各种细胞毒性介质，如活性氧和氮物种（ROS 和 RNS）、丝氨酸和半胱氨酸蛋白酶、膜穿孔剂、基质金属蛋白酶（MMP）、肿瘤坏死因子-α（TNFα）、白细胞介素（IL-1、IL-6、IL-8）、干扰素（IFNs）和酶，如环氧化酶-2（COX-2）、脂氧合酶-5（LOX-5）和磷脂酶 A2（PLA2）等，这些物质被转录因子（如核因子κB（NF-κB）和信号转导和转录激活因子-3（STAT3））激活或激活。本文首先简要综述了肿瘤微环境中存在的主要介质，包括细胞因子、趋化因子、转录因子、类花生酸和激肽，然后概述了炎症在致癌作用的不同阶段中的作用。
