ß-Adrenoreceptors in Human Cancers

Abstract

Cancer is the leading cause of death and represents a significant economic burden worldwide. The numbers are constantly growing as a result of increasing life expectancy, toxic environmental factors, and adoption of Western lifestyle. Among lifestyle factors, stress and the related signaling pathways have recently been implicated in the development of tumors. Here we present some epidemiological and preclinical data concerning stress-related activation of the ß-adrenoreceptors (ß-ARs), which contributes to the formation, sequential transformation, and migration of different tumor cell types. We focused our survey on research results for breast and lung cancer, melanoma, and gliomas published in the past five years. Based on the converging evidence, we present a conceptual framework of how cancer cells hijack a physiological mechanism involving ß-ARs toward a positive modulation of their own survival. In addition, we also highlight the potential contribution of ß-AR activation to tumorigenesis and metastasis formation. Finally, we outline the antitumor effects of targeting the ß-adrenergic signaling pathways, methods for which primarily include repurposed ß-blocker drugs. However, we also call attention to the emerging (though as yet largely explorative) method of chemogenetics, which has a great potential in suppressing tumor growth either by selectively modulating neuronal cell groups involved in stress responses affecting cancer cells or by directly manipulating specific (e.g., the ß-AR) receptors on a tumor and its microenvironment.

Salmonella-induced inhibition of β3-adrenoceptor expression in tumors and reduces tumor metastasis

“…β3-adrenoceptor is overexpressed in tumor cells 4 . Due to Salmonella 's ability to influence the protein expression of tumor cells, we subjected the tumor cell lines to varying multiplicities of infection (M.O.I.)…”

“…The β3-adrenoceptor is involved in obesity and metabolic disorders, but its connection to tumor therapy remains unclear. Recently, the β3-adrenoceptor was found to it overexpressed in tumor cells, and the β3-adrenoceptor plays an essential role in tumor growth, invasion, or metastasis 4 . This finding could potentially have implications for cancer research and treatment strategies.…”

Exploring the causal relationship between antihypertensive drugs and glioblastoma by combining drug target Mendelian randomization study, eQTL colocalization, and single‐cell RNA sequencing

“…Confocal imaging showed that β-AR blockade reduced glioma cell migration by 20% and blood-brain barrier disruption was also significantly reduced. 35 Another study conducted a retrospective cohort study involving 218 patients to investigate the effect of BBs on recurrent GBM. They compared patients who received BBs with patients who did not receive AR-modifying drugs, and both groups were treated with bevacizumab.…”

“…The results showed that the group of rats receiving the β‐AR antagonist survived significantly longer. Confocal imaging showed that β‐AR blockade reduced glioma cell migration by 20% and blood–brain barrier disruption was also significantly reduced 35 . Another study conducted a retrospective cohort study involving 218 patients to investigate the effect of BBs on recurrent GBM.…”