About this Research Topic
Enzymatic and free radical oxidation are common oxidative modification of existing molecules. Lipids are primary targets of this modification because they are the primary repository of oxidizable double bonds. Oxygenated lipids are collectively known as oxylipins. Eicosanoids, including prostaglandins and leukotrienes, represent one of the most biologically important group of oxylipins in mammals. They are biologically active lipids that have been implicated in various pathological processes, such as inflammation and cancer. The synthesis of oxygenated eicosanoids is the result of the coordinated action of several enzymatic activities, from phospholipase A2 that releases the polyunsaturated fatty acids from membrane phospholipids, to primary oxidative enzymes, such as cyclooxygenases and lipoxygenases, to isomerases, synthases and hydrolases that carry out the final synthesis of the biologically active metabolites. The production of arachidonic acid-derived prostanoids and leukotrienes occurs in single cells or takes place in a complex manner in which these biologically active lipids are generated by transcellular biosynthesis through the cooperation of multiple different types of cells in the tumor and inflamed tissues. Inflammation in the tumor microenvironment is now recognized as one of the hallmarks of cancer. Pro-inflammatory eicosanoids are released by different cancer cell types and their surrounding cells. These biologically active lipids can modulate tumor progression through several mechanisms, such as i) by activating their receptors on tumor cells to regulate cell proliferation, apoptosis, migration and invasion and ii) by inducing tumor and stromal cells to secrete growth and angiogenic factors, pro-inflammatory mediators that switch a normal to tumor-supportive microenvironment by promoting angiogenesis and evading attack by the immune system, thus supporting tumor growth and metastasis formation.
Platelets are chief effector cells in haemostasis but they are also inflammatory cells. In fact, they play a central role in the cross-talk with stromal and immune cells leading to their activation which is crucial in the progression of malignant, inflammatory and metabolic diseases. Upon activation, platelets release enhanced levels of lipid mediators [such as thromboxane A2 and prostaglandin E2, generated from arachidonic acid by the activity of cyclooxygenase -1], granule content, including ADP and growth factors, chemokines, proteases and Wnt proteins. Moreover, activated platelets shed different vesicles, such as microparticles and exosomes [rich in genetic material such as mRNAs and miRNAs (endogenous RNAs that can play important regulatory roles by targeting mRNAs for cleavage or translational repression)]. Platelet-derived products induce in cancer cells several phenotypic changes promoting tumor development and metastasis. All these aspects make the study of the role of eicosanoids in health and disease one of the most active fields of translational research nowadays and suggest that the profiling of these biologically active lipids in each patient may be a crucial step for a personalized therapeutic approach and for the assessment of drug response during treatment.
Thus, the aim of this Frontiers Research Topic is to gather a group of researchers with outstanding expertise in the study of the role of lipid mediators in health and disease for the collection of scientific articles covering the spectrum of all the mentioned aspects of this charming field.
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.