An Increased Expression of Cysteinyl Leukotriene 2 Receptor in Colorectal Adenocarcinomas Correlates with High Differentiation

Magnusson, Cecilia; Ehrnström, Roy; Olsen, Jørgen; Sjölander, Anita

doi:10.1158/0008-5472.can-07-0771

Cited by 41 publications

(66 citation statements)

References 52 publications

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“…19 Several groups have demonstrated the modulation of CysLT receptors by cytokines and inflammatory stimuli. 49,50 Thivierge et al 25 demonstrated that human monocytes express both CysLT1 and CysLT2 receptors similarly and their differentiation in DCs inhibits the expression of CysLT1, whereas their maturation with 200 ng/ml LPS increases CysLTR2 expression. In contrast, upon activation of DCs by LPS (1 lg/ml) no variations in the expression of CysLRT1 were observed but there is a greater reduction of CysLRT2.…”

Section: Discussionmentioning

confidence: 99%

“…In this sense, it has been demonstrated in several tissues that the expression of both receptors can be regulated by CysLT release. 18,50 The use of montelukast did not allow us to block the production of IL-23, indicating that it could be modulated by the action of LTC 4 through the CysLTR2. This point could not be evaluated; because there is still no specific receptor antagonist.…”

Section: Discussionmentioning

confidence: 99%

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Leukotriene C4 prevents the complete maturation of murine dendritic cells and modifies interleukin-12/interleukin-23 balance

Álvarez¹,

Amaral²,

Langellotti³

et al. 2011

Immunology

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Summary Leukotriene C4 is an important mediator in the development of inflammatory reactions and ischaemia. Previous studies have shown that leukotriene C4 is able to modulate the function of dendritic cells (DCs) and induce their chemotaxis from skin to lymph node. In this study, we decided to evaluate the modulation exerted by leukotriene C4 on DCs, depending on their status of activation. We showed for the first time that leukotriene C4 stimulates endocytosis both in immature and lipopolysaccharide (LPS) ‐activated DCs. Moreover, it suppressed the interleukin‐12p70 (IL‐12p70) release, but induces the secretion of IL‐23 by DCs activated with LPS and promotes the expansion of T helper type 17 (Th17) lymphocytes. Furthermore, blocking the release of IL‐23 reduced the percentages of CD4+ T cells producing IL‐17 in a mixed lymphocyte reaction. Ours results suggest that leukotriene C4 interferes with the complete maturation of inflammatory DCs in terms of phenotype and antigen uptake, while favouring the release of IL‐23, the main cytokine involved in the maintenance of the Th17 profile.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Leukotriene C4 prevents the complete maturation of murine dendritic cells and modifies interleukin-12/interleukin-23 balance

Álvarez¹,

Amaral²,

Langellotti³

et al. 2011

Immunology

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“…High expression of the BLT 1 receptor [19] and the CystLT 1 receptor was detected in human colon cancer tissues, whereas CysLT 2 receptor expression was reduced in colon cancer and was associated with poor prognosis, due to its capacity to induce differentiation and growth inhibition [18]. Thus, the CysLT 2 receptor could have more anti-tumorigenic activity than the CysLT 1 receptor in intestinal epithelial cells, and the balance between the two receptors is important for the outcome of tumor progression.…”

Section: Role Of Eicosanoids In the Control Of Intestinal Epithelial mentioning

confidence: 99%

“…With respect to the presence of LT receptors in the intestine, the CysLT 1 receptor is expressed in intestinal epithelial cells and tumorderived intestinal cells [15] whereas the CysLT 2 receptor is expressed in differentiated intestinal epithelial cells but not in tumor-derived intestinal cell lines [18]. The BLT 1 receptor is also expressed in human colon cancer cell lines and colon cancer tissue but not in normal colon tissue [19].…”

mentioning

confidence: 99%

Role of eicosanoids on intestinal epithelial homeostasis

Ferrer

Moreno

2010

Biochemical Pharmacology

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The intestinal epithelium is a highly dynamic system that is continuously renewed by a process involving cell proliferation and differentiation. Moreover, it is the main interface with the external environment, and maintenance and regulation of the epithelial structure and epithelial barrier function are key determinants of digestive health and host well-being. The tight junction, a multiprotein complex composed of transmembrane proteins associated with the cytoskeletal peri-junctional ring of actin and myosin, is an essential component of this barrier that is strictly regulated in a spatio-temporal manner by a complex signaling network. Defects in the intestinal epithelial barrier function have been observed in inflammatory bowel disease, and a classic example of the connection between inflammation and cancer is the increased risk of colorectal cancer in patients with inflammatory bowel disease. In recent years, several molecules have emerged as critical players contributing to inflammationassociated colorectal cancer. For example, eicosanoids derived from arachidonic acid are proposed as mediators involved in the regulation of epithelial structure/function. Interestingly, the tissue concentration of eicosanoids increases during mucosal inflammation and colorectal cancer development. This overview focuses on the physiological and physiopathological roles of eicosanoids in cell growth/cell differentiation/apoptosis and in the paracellular permeability of the intestinal epithelium. A better understanding of these processes will foster new ideas for the development of therapies for these chronic disorders.

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“…Interestingly, an inhibition of either COX or 5-LOX alone resulted in the activation of the other pathway, and consequently, combined treatment with COX and 5-LOX inhibitors produced greater inhibition of tumor cell proliferation. A high expression of the BLT 1 receptor of LTB 4 (Ihara et al, 2007) and the CystLT 1 receptor of LTD 4 was detected in human colon cancer tissues, whereas CysLT 2 receptor expression was reduced in colon cancer and was associated with poor prognosis, due to its capacity to induce differentiation and growth inhibition (Magnusson et al, 2007). Recently, we observed that several LOX metabolites from AA and linoleic acid such as LTB 4 , LTD 4 , 5-HETE, 12-HETE, 15-HETE and 13-hydroxyoctadecanoic acid are involved in the control of CRC cell line proliferation (Cabral et al, 2013;Cabral et al, 2014;Martín-Venegas et al, 2014;Cabral et al, 2015).…”

Section: Role Of the Arachidonic Acid Cascade On Intestinal Epitheliamentioning

confidence: 99%

Effect of extra virgin olive oil components on the arachidonic acid cascade, colorectal cancer and colon cancer cell proliferation

Storniolo

2016

Grasas y Aceites

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SUMMARY:The mediterranean diet (MD) reduced the risk of colorectal cancer (CRC), and olive oil, the primary source of fat in the MD, has also been found to have a protective effect. However, animals fed with oleic acid present a high number of intestinal tumours, suggesting that oleic acid and olive oil consumption can exert different effects on CRC. Considering that extra virgin olive oil (EVOO) is a complex mix of fatty acids and minor compounds such as polyphenols, hydrocarbons, phytosterols and triterpenes; and that these compounds have antioxidant activity and consequently they can modulate the arachidonic acid (AA) cascade and eicosanoid synthesis. This review analyzes the state of the art of olive oil components on the AA cascade and cellular mechanism involved in CRC such as intestinal epithelial cell growth/apoptosis, to understand the fact that the consumption of seed oils with high oleic content or EVOO will probably have different effects on CRC development.KEYWORDS : Cell growth; Colorectal cancer; Eicosanoid; Oleic acid; Oxidative stress; Polyphenol RESUMEN: Efecto de los componentes del aceite de oliva virgen extra en la cascada del ácido araquidónico, el cáncer colorrectal y la proliferación de células de cáncer de colon. La dieta Mediterranea (DM) y el aceite de oliva reducen el riesgo de cáncer colorrectal (CCR). Sin embargo, animales alimentados con dietas ricas en ácido oleico presentan un elevado número de tumores intestinales, lo que sugiere que el consumo de ácido oleico y aceite de oliva pueden tener efectos diferentes sobre el desarrollo de CCR. Considerando que el aceite de oliva extra virgen (AOEV) es una compleja mezcla de ácidos grasos y compuestos minoritarios como polifenoles, lignanos, hidrocarburos, fitoesteroles y triterpenos; y que algunos de estos compuestos son antioxidantes y modulan la cascada del ácido araquidónico (AA) y la producción de eicosanoides. Analizamos la información existente sobre el efecto de los componentes del AOEV sobre la cascada del AA y los mecanismos implicados en el CCR como el crecimiento de las células epiteliales intestinales/apoptosis, lo que nos permitirá entender por qué el consumo de aceites de semillas altos en oleico o AOEV probablemente tendrán diferentes efectos sobre el desarrollo del CCR.

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An Increased Expression of Cysteinyl Leukotriene 2 Receptor in Colorectal Adenocarcinomas Correlates with High Differentiation

Cited by 41 publications

References 52 publications

Leukotriene C4 prevents the complete maturation of murine dendritic cells and modifies interleukin-12/interleukin-23 balance

Leukotriene C4 prevents the complete maturation of murine dendritic cells and modifies interleukin-12/interleukin-23 balance

Role of eicosanoids on intestinal epithelial homeostasis

Effect of extra virgin olive oil components on the arachidonic acid cascade, colorectal cancer and colon cancer cell proliferation

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