Volume 2, 2019
Disruption of homeostasis-induced signaling and crosstalk in the carcinogenesis paradigm “Epistemology of the origin of cancer”
|Number of page(s)||34|
|Section||Life Sciences - Medicine|
|Published online||25 April 2019|
Eicosanoids in carcinogenesis
Theodor-Billroth-Academy®, Germany, USA
2 INCORE, International Consortium of Research Excellence of the Theodor-Billroth-Academy®, Germany, USA
3 Department of Surgery, Carl-Thiem-Klinikum, Cottbus, Germany
4 Risk-Based Decisions Inc., Sacramento, CA, USA
* Corresponding author: firstname.lastname@example.org
Accepted: 16 December 2018
Inflammation is the body's reaction to pathogenic (biological or chemical) stimuli and covers a burgeoning list of compounds and pathways that act in concert to maintain the health of the organism. Eicosanoids and related fatty acid derivatives can be formed from arachidonic acid and other polyenoic fatty acids via the cyclooxygenase and lipoxygenase pathways generating a variety of pro- and anti-inflammatory mediators, such as prostaglandins, leukotrienes, lipoxins, resolvins and others. The cytochrome P450 pathway leads to the formation of hydroxy fatty acids, such as 20-hydroxyeicosatetraenoic acid, and epoxy eicosanoids. Free radical reactions induced by reactive oxygen and/or nitrogen free radical species lead to oxygenated lipids such as isoprostanes or isolevuglandins which also exhibit pro-inflammatory activities. Eicosanoids and their metabolites play fundamental endocrine, autocrine and paracrine roles in both physiological and pathological signaling in various diseases. These molecules induce various unsaturated fatty acid dependent signaling pathways that influence crosstalk, alter cell–cell interactions, and result in a wide spectrum of cellular dysfunctions including those of the tissue microenvironment. Although the complete role of eicosanoids, including that of the recently elucidated anti-inflammatory specialized pro-resolving lipid mediators (SPMs), e.g. lipoxins, resolvins, protectins and maresins, is not completely understood, the result of unremitting chronic inflammation is fostering early stages of carcinogenesis. Chronic inflammation facilitates the transition from a normal cell to a cancerous one. The disruption of homeostasis across a wide, but identifiable, swath of diverse molecular pathways creates a micromilieu which constitutes an early and necessary step in the 6-step sequence of carcinogenesis for the vast majority of cancers, termed “sporadic cancers”.
Key words: 20-HETE / Cancer / Carcinogenesis / Cell transition / Chronic inflammation / Cyclooxygenase / Cox / EET / Eicosanoids / Epidemiology / Epigenetics / Fibrosis / Genomics / Leukotrienes / microRNA / Mutation / Pathogenesis / Precancerous niche / Proteomics / Reactive oxygen species / ROS / Somatic mutation
© B.L.D.M. Brücher and I.S. Jamall, Published by EDP Sciences 2019
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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