More Evidence that Norepinephrine and β3-Adrenoreceptors May Drive Melanoma Progression & Aggressiveness

More Evidence that Norepinephrine and β3-Adrenoreceptors May Drive Melanoma Progression & Aggressiveness

A report recently published in Oncotarget shows that the β3-adrenoreceptors are involved in melanoma aggressiveness, and that these receptors, expressed on several accessory cells, may orchestrate their function and thus, sustain melanoma progression.

Recent research indicates that stress and stress mediators contribute to cancer development and/or progression.

It appears that in this process a major role is being played by the sympathetic nervous system through the effects of catecholamines, mainly norepinephrine (noradrenaline) and the beta-adrenergic system. The list of various tumors affected by catecholamines is rapidly growing, and this includes melanoma (Colucci R & Moretti S, J Cancer Res Clin Oncol. 2015 Nov 23).

In the Oncotarget study, Maura Calvani and colleagues from the University of Florence, Tuscany Tumor Institute, Florence, Italy demonstrate that β3-adrenoreceptors are expressed in human melanocytic lesions but also in stromal, endothelial and inflammatory cells, and that this expression positively correlated with melanoma malignancy.

Importantly, tumor-associated accessory cells appeared to sustain secretion of proinflammatory cytokines and to drive de novo angio/vasculogenesis. This included the production of inteleukin (IL-6), IL-8 and vascular endothelial growth factor (VEGF)-A, and a role of β3-adrenoreceptors in the recruitment of fibroblasts, monocytes, bone marrow precursors (MSCs) and endothelial cells.

These observations substantiate previous work suggesting the involvement of catecholamines in melanoma progression. This includes the ability of norepinephrine to upregulates VEGF, IL-8, and IL-6 expression in human melanoma tumor cell lines.

Of note, this study suggests that β-adrenoreceptor blockers may provide new therapeutic opportunities in melanoma, and, as we previously discussed, in general, beta blockers hold substantial potential for therapeutical interventions in cancer.

Source: Oncotarget. 2015, 6:4615-32.
Read More: ncbi.nlm.nih.gov

Source: Cover Image: The β2-adrenoceptor (blue) coupling to the heterotrimeric G protein GS (red, yellow, green) after binding of an agonist. Author: Brian Kobilka, Stanford University School of Medicine; https://en.wikipedia.org/wiki/History_of_catecholamine_research#/media/File:Receptor.kobilka.jpg Credit: Wikimedia Commons.

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