Back to Search
Start Over
β(3)‐Adrenoceptor as a potential immuno‐suppressor agent in melanoma
- Source :
- Br J Pharmacol
- Publication Year :
- 2019
- Publisher :
- John Wiley and Sons Inc., 2019.
-
Abstract
- BACKGROUND AND PURPOSE: Stress‐related catecholamines have a role in cancer and β‐adrenoceptors; specifically, β(2)‐adrenoceptors have been identified as new targets in treating melanoma. Recently, β(3)‐adrenoceptors have shown a pleiotropic effect on melanoma micro‐environment leading to cancer progression. However, the mechanisms by which β(3)‐adrenoceptors promote this progression remain poorly understood. Catecholamines affect the immune system by modulating several factors that can alter immune cell sub‐population homeostasis. Understanding the mechanisms of cancer immune‐tolerance is one of the most intriguing challenges in modern research. This study investigates the potential role of β(3)‐adrenoceptors in immune‐tolerance regulation. EXPERIMENTAL APPROACH: A mouse model of melanoma in which syngeneic B16‐F10 cells were injected in C57BL‐6 mice was used to evaluate the effect of β‐adrenoceptor blockade on the number and activity of immune cell sub‐populations (Treg, NK, CD8, MDSC, macrophages, and neutrophils). Pharmacological and molecular approaches with β‐blockers (propranolol and SR59230A) and specific β‐adrenoceptor siRNAs targeting β(2)‐ or β(3)‐adrenoceptors were used. KEY RESULTS: Only β(3)‐, but not β(2)‐adrenoceptors, were up‐regulated under hypoxia in peripheral blood mononuclear cells and selectively expressed in immune cell sub‐populations including Treg, MDSC, and NK. SR59230A and β(3)‐adrenoceptor siRNAs increased NK and CD8 number and cytotoxicity, while they attenuated Treg and MDSC sub‐populations in the tumour mass, blood, and spleen. SR59230A and β(3)‐adrenoceptor siRNAs increased the ratio of M1/M2 macrophages and N1 granulocytes. CONCLUSIONS AND IMPLICATIONS: Our data suggest that β(3)‐adrenoceptors are involved in immune‐tolerance, which opens the way for new strategic therapies to overcome melanoma growth. LINKED ARTICLES: This article is part of a themed section on Adrenoceptors—New Roles for Old Players. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.14/issuetoc
- Subjects :
- 0301 basic medicine
Male
Skin Neoplasms
Cell Survival
Cell
Adrenergic beta-Antagonists
Melanoma, Experimental
Peripheral blood mononuclear cell
Immune tolerance
03 medical and health sciences
Mice
0302 clinical medicine
Immune system
medicine
Tumor Cells, Cultured
Animals
Receptor
Cell Proliferation
Pharmacology
Themed Section: Research Paper
business.industry
Melanoma
Cancer
medicine.disease
Coculture Techniques
Mice, Inbred C57BL
Disease Models, Animal
030104 developmental biology
medicine.anatomical_structure
Receptors, Adrenergic, beta-3
Cancer research
business
030217 neurology & neurosurgery
CD8
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Br J Pharmacol
- Accession number :
- edsair.doi.dedup.....3ed7a11a5d3bb680f2dbb7b13c3a5182