RESUMEN
5-lipoxygenase is an enzyme responsible for the synthesis of a range of bioactive lipids signalling molecules known collectively as eicosanoids. 5-lipoxygenase metabolites such as 5-hydroxyeicosatetraenoic acid (5-HETE) and a number of leukotrienes are mostly derived from arachidonic acid and have been shown to be lipid mediators of inflammation in different pathological states including cancer. Upregulated 5-lipoxygenase expression and metabolite production is found in a number of cancer types and has been shown to be associated with increased tumorigenesis. 5-lipoxygenase activity is present in a number of diverse cell types of the immune system and connective tissue. In this review, we discuss potential routes through which cancer cells may utilise the 5-lipoxygenase pathway to interact with the tumour microenvironment during the development and progression of a tumour. Furthermore, immune-derived 5-lipoxygenase signalling can drive both pro- and anti-tumour effects depending on the immune cell subtype and an overview of evidence for these opposing effects is presented.
Asunto(s)
Araquidonato 5-Lipooxigenasa/metabolismo , Comunicación Celular , Neoplasias/metabolismo , Neoplasias/patología , Transducción de Señal , Microambiente Tumoral , Tejido Adiposo/inmunología , Tejido Adiposo/metabolismo , Animales , Vías Biosintéticas/efectos de los fármacos , Ciclooxigenasa 2/metabolismo , Fibroblastos/inmunología , Fibroblastos/metabolismo , Fibroblastos/patología , Humanos , Inmunomodulación , Leucotrienos/biosíntesis , Metabolismo de los Lípidos , Linfocitos/inmunología , Linfocitos/metabolismo , Células Mieloides/inmunología , Células Mieloides/metabolismo , Neoplasias/inmunología , Neovascularización Patológica/inmunología , Neovascularización Patológica/metabolismo , Microambiente Tumoral/inmunología , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
In the midst of a worsening obesity epidemic, the incidence of obesity-associated morbidities, including cancer, diabetes, cardiac and liver disease is increasing. Insights into mechanisms underlying pathological obesity-associated inflammation are lacking. Both the omentum, the principal component of visceral fat, and liver of obese individuals are sites of excessive inflammation, but to date the T cell profiles of both compartments have not been assessed or compared in a patient cohort with obesity-associated disease. We have previously identified that omentum is enriched with inflammatory cytokines, chemokines and T cells. Here, we compared the inflammatory profile of T cells in the omentum and liver of patients with the obesity-associated malignancy oesophageal adenocarcinoma (OAC). Furthermore, we assessed the secreted cytokine profile in OAC patient serum, omentum and liver to assess systemic and local inflammation. We observed parallel T cell cytokine profiles and phenotypes in the omentum and liver of OAC patients, in particular CD69(+) and inflammatory effector memory T cells. This study reflects similar processes of inflammation and T cell activation in the omentum and liver, and may suggest common targets to modulate pathological inflammation at these sites.