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Injection of Syngeneic Murine Melanoma Cells to Determine Their Metastatic Potential in the Lungs

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β₃ -Adrenoceptor as a potential immuno-suppressor agent in melanoma

Maura Calvani¹, Gennaro Bruno², Massimo Dal Monte³

¹Oncohematology Unit, Department of Pediatric Oncology, Meyer University Children's University Hospital, Florence, Italy.

British Journal of Pharmacology

|March 16, 2019

Abstract

Background And Purpose:

Stress-related catecholamines have a role in cancer and β-adrenoceptors; specifically, β₂ -adrenoceptors have been identified as new targets in treating melanoma. Recently, β₃ -adrenoceptors have shown a pleiotropic effect on melanoma micro-environment leading to cancer progression. However, the mechanisms by which β₃ -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 β₃ -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 β₂ - or β₃ -adrenoceptors were used.

Key Results:

Only β₃ -, but not β₂ -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 β₃ -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 β₃ -adrenoceptor siRNAs increased the ratio of M1/M2 macrophages and N1 granulocytes.

Conclusions And Implications:

Our data suggest that β₃ -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.

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