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Received Apr 4, 2017; Revised Jun 22, 2017; Accepted Aug 24, 2017
This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
1. Introduction
Chronic inflammation is associated with high incidence of various types of cancer, including cervical, gastric, and intestinal cancers [1]. In response to inflammatory stimuli, leucocytes release reactive oxygen and nitrogen species that cause DNA lesions, including oxidized bases, single and double DNA breaks, which lead to genome instability. Probability of tumor formation increases with the accumulation of mutations in oncogenes and/or tumor suppressor genes [2–4].
Malignant cells created inflammatory microenvironment by releasing inflammatory cytokines and chemokines, in particular interleukin- (IL-) 8 (CXCL8). CXCL8 recruits leukocytes, such as monocytes and neutrophils, into tumor microenvironment. Infiltrated macrophages and neutrophils, in their turn, release growth factors and proteases that promote angiogenesis and tumor metastasis. The level of tumor-associated macrophage and neutrophil infiltration closely correlates with poor prognosis in breast, prostate, lung, and melanoma cancers [5–9].
CXCL8 is a member of inflammatory chemokine family that promotes chemotaxis by activating CXCR1 or CXCR2 receptors on targeted cells [10–12]. These receptors are expressed in neutrophils, monocytes, mast cells, eosinophils, natural killer (NK) cells, and activated CD8+ T cells [13–16]. CXCL8 mediates recruitment of these immune cells and endothelial progenitor cells, regulating inflammation, angiogenesis, and wound healing. In cancer, CXCL8 promotes tumor cell proliferation and migration, angiogenesis, and metastasis [17–21].
CXCL8 is overexpressed in multiple cancer types, including nonsmall cell lung cancer (NSCLC) [22, 23], breast [24, 25], pancreatic [26], and colorectal cancers [21]. In clinical studies, patients with high CXCL8 levels are reported to have poorer prognosis: lower survival rate, higher liability of tumor recurrence after surgery excision, and higher liability of tumor metastasis to distant organs [26]. Therefore, CXCL8 can be used as a predictor for tumor prognosis, at least for pancreatic [26] and colorectal cancers [27].
CXCL8 expression is regulated primarily by three transcription factors:...