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Beta-adrenergic receptors are expressed across diverse cancers
Steven L Rains1, Clarissa N Amaya1, Brad A Bryan1
1Department of Biomedical Sciences, Texas Tech University Health Sciences Center, El Paso, TX, USA.
Abstract:
Based largely on retrospective analyses and a handful of prospective case reports, pharmacological inhibition of the beta adrenergic receptors using beta blockers has shown clinical anti-cancer efficacy in reproductive cancers, as well as angiosarcoma and multiple myeloma. Because of the potential promise of beta blockers as an adjunct to standard anti-cancer therapy, it is imperative to identify other tumor types expressing beta adrenergic (β-AR) receptors so future preclinical and clinical studies can be directed at the most promising tumor targets. We performed immunohistochemical detection of β1-AR, β2-AR, and β3-AR across 29 of the most common human cancer types (389 tissues total) and 19 matching non-diseased controls (100 tissues total). Our analysis revealed all three β-AR receptors were expressed most strongly in melanoma relative to other cancer types. Other malignancies that revealed relatively higher levels of β-AR receptors were esophagus, pancreas, kidney, and lung cancers. Moreover, particular β-AR receptors exhibited significant overexpression in tumor tissue relative to their matching normal tissue in urogenital/reproductive malignancies including breast, endometrium, ovarian, and urothelial cancer, as well as colon, lung, and thyroid cancer. This study identifies several cancer types expressing the β-AR receptors which should be evaluated in future studies for susceptibility to beta blockade.
Insights
Beta blockers show anti-cancer effects by inhibiting beta adrenergic receptors (β-ARs). This study found melanoma, esophagus, pancreas, kidney, and lung cancers highly express these receptors, suggesting new therapeutic targets.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Pharmacological inhibition of beta adrenergic receptors (β-ARs) using beta blockers demonstrates anti-cancer efficacy in certain cancers.
- Identifying additional cancer types expressing β-ARs is crucial for developing novel adjunct therapies.
Purpose of the Study:
- To investigate the expression of β1-AR, β2-AR, and β3-AR across common human cancer types.
- To identify potential new cancer targets for beta blocker therapy.
Main Methods:
- Immunohistochemical detection of β1-AR, β2-AR, and β3-AR.
- Analysis of 389 tumor tissues from 29 common human cancer types and 100 matching non-diseased control tissues.
Main Results:
- All three β-AR subtypes were most strongly expressed in melanoma compared to other cancers.
- Elevated β-AR expression was observed in esophagus, pancreas, kidney, and lung cancers.
- Significant β-AR overexpression in tumor versus normal tissue was noted in breast, endometrium, ovarian, urothelial, colon, lung, and thyroid cancers.
Conclusions:
- Melanoma, esophagus, pancreas, kidney, and lung cancers exhibit high β-AR expression.
- Several urogenital/reproductive and other cancers show significant β-AR overexpression.
- These findings identify promising cancer types for future studies evaluating beta blocker susceptibility.
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