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The Role of the Mediators of Inflammation in Cancer Development

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Pathology & Oncology Research

Abstract

Epigenetic disorders such as point mutations in cellular tumor suppressor genes, DNA methylation and post-translational modifications are needed to transformation of normal cells into cancer cells. These events result in alterations in critical pathways responsible for maintaining the normal cellular homeostasis, triggering to an inflammatory response which can lead the development of cancer. The inflammatory response is a universal defense mechanism activated in response to an injury tissue, of any nature, that involves both innate and adaptive immune responses, through the collective action of a variety of soluble mediators. Many inflammatory signaling pathways are activated in several types of cancer, linking chronic inflammation to tumorigenesis process. Thus, Inflammatory responses play decisive roles at different stages of tumor development, including initiation, promotion, growth, invasion, and metastasis, affecting also the immune surveillance. Immune cells that infiltrate tumors engage in an extensive and dynamic crosstalk with cancer cells, and some of the molecular events that mediate this dialog have been revealed. A range of inflammation mediators, including cytokines, chemokines, free radicals, prostaglandins, growth and transcription factors, microRNAs, and enzymes as, cyclooxygenase and matrix metalloproteinase, collectively acts to create a favorable microenvironment for the development of tumors. In this review are presented the main mediators of the inflammatory response and discussed the likely mechanisms through which, they interact with each other to create a condition favorable to development of cancer.

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Abbreviations

AA:

Arachidonic acid

AP-1:

Activator protein 1

APC:

Antigen-presenting cell

cAMP:

Cyclic AMP

CCL:

Chemokine (C-C motif) ligand

CD:

Cluster of differentiation

cHL:

Classical Hodgkin lymphoma

CLRs:

C-type lectin receptors

COX:

Cyclooxygenase

CRC:

Colorectal cancer

CXC:

Chemokine receptors

DAMPs:

Damage-associated molecular patterns

DNA:

Deoxyribonucleic acid

ECM:

Extracellular matrix

EGF:

Epidermal growth factor

EGFR:

Epidermal growth factor receptor

EMT:

Epithelial-mesenchymal transition

FOXP3:

Forkhead box P3

GPCRs:

G protein-coupled

HPV:

Human papillomavirus

ICC:

Invasive cervical cancer

IFN:

Interferon

IL:

Interleukin

MHC:

Major histocompatibility complex

miRNAs:

MicroRNAs

MM:

Multiple myeloma

MMPs:

Enzymes matrix metalloproteinase matrix

NF-κB:

Nuclear factor kappa-light-chain-enhancer of activated B cells

NK:

Natural killer cell

NLRs:

NOD-like receptors

NO:

Nitric oxide

NSAIDs:

Non-steroidal anti-inflammatory drugs

p53:

Tumor protein p53

PAMPs:

Pathogen-associated molecular patterns

PGs:

Prostaglandins

PRRs:

Pattern recognition receptors

PTGER:

Prostaglandin receptor

PTGES:

Terminal prostaglandin synthase enzyme

PubMed:

US National Library of Medicine

RLRs:

RIG-like receptors

ROS:

Reactive oxygen species

STAT:

Signal transducers and activators of transcription

TCR:

T Cell Receptor

TGF:

Transforming growth factor

Th cells:

T helper cells

TLRs:

Toll-like receptors

TNF:

Tumor necrosis factor

Tregs:

Regulatory T cells

Txs:

Thromboxanes

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Conflict of Interest

All authors state that there are no conflicts of interest to be declared. No financial support was requested or received in the production of this paper.

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Authors and Affiliations

  1. Post-Graduate Program in Biological Sciences, Federal University of Rio Grande do Norte, Natal, RN, Brazil

    José Veríssimo Fernandes & Josélio Maria Galvão de Araújo

  2. Department of Microbiology and Parasitology, Federal University of Rio Grande do Norte, Campus Universitário, 59072-910, Natal, RN, Brazil

    José Veríssimo Fernandes & Josélio Maria Galvão de Araújo

  3. Maternidade Escola Januário Cicco, Federal University of Rio Grande do Norte, Natal, RN, Brazil

    Ricardo Ney Oliveira Cobucci

  4. Department of Pathology, Federal University of Rio Grande do Norte, Natal, RN, Brazil

    Carlos André Nunes Jatobá

  5. Department of Biomedical Sciences, University of Rio Grande do Norte State, Mossoró, RN, Brazil

    Thales Allyrio Araújo de Medeiros Fernandes

  6. Hospital Universitário, Federal University of Triângulo Mineiro, Mina Gerais, Brazil

    Judson Welber Veríssimo de Azevedo

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  1. José Veríssimo Fernandes
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  2. Ricardo Ney Oliveira Cobucci
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  3. Carlos André Nunes Jatobá
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  4. Thales Allyrio Araújo de Medeiros Fernandes
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Correspondence to José Veríssimo Fernandes.

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Fernandes, J.V., Cobucci, R.N.O., Jatobá, C.A.N. et al. The Role of the Mediators of Inflammation in Cancer Development. Pathol. Oncol. Res. 21, 527–534 (2015). https://doi.org/10.1007/s12253-015-9913-z

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