β-Adrenergic system, a backstage manipulator regulating tumour progression and drug target in cancer therapy

Tang, Jing; Li, Zhijie; Lü, Lei; Cho, Chi Hin

doi:10.1016/j.semcancer.2013.08.009

Cited by 143 publications

(149 citation statements)

References 111 publications

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“…Beta-adrenergic system is comprised of catecholamines (Tang et al, 2013), and beta-adrenergic receptor is composed of three subtypes, β1, β2 and β3 (Yamazaki et 1 * al., 2014). In preclinical studies, researchers had observed the expression of beta-adrenergic receptors in a few breast cancer cell lines and human breast cancer tissue samples (Madden et al, 2011;Park et al, 2011;Powe et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

β-Adrenergic Receptors : New Target in Breast Cancer

Wang

et al. 2016

Asian Pacific Journal of Cancer Prevention

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Background: Preclinical studies have demonstrated that β-adrenergic receptor antagonists could improve the prognosis of breast cancer. However, the conclusions of clinical and pharmacoepidemiological studies have been inconsistent. This review was conducted to re-assess the relationship between beta-adrenoceptor blockers and breast cancer prognosis. Materials and Methods: The literature was searched from PubMed, EMBASE and Web of Nature (Thompson Reuters) databases through using key terms, such as breast cancer and betaadrenoceptor blockers. Results: Ten publications met the inclusion criteria. Six suggested that receiving betaadrenoceptor blockers reduced the risk of breast cancer-specific mortality, and three of them had statistical significance (hazard ratio (HR)=0.42; 95% CI=0.18-0.97; p=0.042). Two studies reported that risk of recurrence and distant metastasis (DM) were both significantly reduced. One study demonstrated that the risk of relapsefree survival (RFS) was raised significantly with beta-blockers (BBS) (HR= 0.30; 95% CI=0.10-0.87; p=0.027). One reported longer disease-free interval (Log Rank (LR)=6.658; p=0.011) in BBS users, but there was no significant association between overall survival (OS) and BBS (HR= 0.35; 95% CI=0.12-1.0; p=0.05) in five studies. Conclusions: Through careful consideration, it is suggested that beta-adrenoceptor blockers use may be associated with improved prognosis in breast cancer patients. Nevertheless, larger size studies are needed to further explore the relationship between beta-blocker drug use and breast cancer prognosis.

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Section: Introductionmentioning

confidence: 99%

β-Adrenergic Receptors : New Target in Breast Cancer

Wang

et al. 2016

Asian Pacific Journal of Cancer Prevention

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“…Notably, retrospective studies have shown that breast cancer patients taking a b-blocker for other purposes have decreased cancer reoccurrence and increased survival. 15,[20][21][22][23][24][25][26][27][28][29] Clinical trials have been initiated to examine whether treatment of breast cancer patients with b-blockers decreases the chance of reoccurrence.…”

Section: Introductionmentioning

confidence: 99%

β-Adrenergic receptors suppress Rap1B prenylation and promote the metastatic phenotype in breast cancer cells

Wilson

Lorimer

Tyburski

et al. 2015

Cancer Biology & Therapy

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Keywords: adenosine receptor, breast cancer, cholera toxin, G protein-coupled receptor, protein isoprenylation, protein kinase A (PKA), Ras-related protein 1 (Rap1), b-adrenergic receptor Abbreviations: Adenosine 2B Receptor (A 2 BR), b-adrenergic receptor (bAR), Bay 60-6583 (Bay), Cholera toxin (Ctx), half time (T 1/2 ), Isoproterenol (Iso), G protein-coupled receptors (GPCR), Phosphate buffered saline (PBS), Protein kinase A (PKA), Propranolol (Prop).A greater understanding of the molecular basis of breast cancer metastasis will lead to identification of novel therapeutic targets and better treatments. Rap1B is a small GTPase that suppresses the metastasis of breast cancer cells by increasing cell-cell adhesion. In breast cancer, a decrease in Rap1B prenylation and subsequent loss of Rap1B at the plasma membrane decreases cell-cell adhesion and increases cell scattering, which promotes the metastatic phenotype. Protein kinase A (PKA) was recently found to phosphorylate Rap1B and inhibit its prenylation. PKA is activated by G protein-coupled receptors (GPCR) that stimulate Ga s . In this study, we investigated whether the general Ga s activator, cholera toxin, and agonists of the b-adrenergic receptor (bAR), which is a Ga s -coupled GPCR, promote Rap1B phosphorylation and inhibit its prenylation. We show here that cholera toxin and bAR activation phosphorylate Rap1B and inhibit its prenylation and membrane localization, reducing cell-cell adhesion and promoting cell scattering. Furthermore, we report that breast cancer cell migration is decreased by the FDA-approved b-blocker, propranolol. Pharmacological targeting of GPCRs, especially those such as the bAR that are regulated by FDA-approved drugs, to increase cell adhesion and decrease cell scattering could provide a promising therapeutic approach to reduce breast cancer metastasis.

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“…Based on these facts, it has been suggested that interventions reducing the eff ect of the sympathetic neurotransmitters may represent a potential adjuvant therapy in oncological patients (Schuller 2010;Powe and Entschladen 2011;Tang et al 2013). Th ese interventions may be useful also for the secondary micro metastasis development prevention aft er surgical extirpation of the primary tumor mass (Glasner et al 2010;Neeman et al 2012).…”

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confidence: 99%

Sympathectomized tumor-bearing mice survive longer but develop bigger melanomas

Horváthová

Tillinger

Padová

et al. 2016

Endocrine Regulations

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Objectives.Previously we have shown that 20 days aft er the tumor cells injection smaller melanomas have been developed in chemically sympathectomized mice in comparison with animals having intact sympathetic nervous system. However, it is known that chemical sympathectomy reduces the sympathetic neurotransmission only temporarily. In the present study, we monitored the survival of the sympathectomized mice with melanoma with an attempt to fi nd out how long the suppressing eff ect of sympathectomy on the melanoma growth may endure.Methods. Th e chemical sympathectomy was performed by intraperitoneal injection of neurotoxin 6-hydroxydopamine in male C57BL/6J mice. Seven days later, the animals were injected subcutaneously with B16-F10 melanoma cells. Th en, melanoma development, survival of the tumorbearing mice and weight of the developed tumor mass were analyzed.Results. Sympathectomy delayed the development of the palpable tumors (18th day vs.14th day) and signifi cantly prolonged the survival of the tumor-bearing mice (median 34 days vs. 29 days). However, the weight of the developed melanoma was signifi cantly increased in the sympathectomized mice in comparison with the animals having intact sympathetic nervous system.Conclusions. Th e data of the present study showed that eff ect of the chemical sympathectomy, performed before the tumor growth induction, persisted even at the time when sympathetic nerves started to regenerate that resulted in a prolonged survival of the mice with melanoma. However, comparing to our previous study, in which we have shown a reduced tumor mass in earlier stages of the tumor growth, specifi cally 20 days aft er melanoma cells injection, now we indicate that in later stages of the melanoma progression, the tumor mass was signifi cantly increased in sympathectomized animals. Th ese contra-intuitive fi ndings may indicate that interventions aff ecting the sympathetic nervous system may exert complex eff ect on the tumor progression. Based on these data we may suggest that the potential therapeutic interventions aff ecting the sympathetic signaling in the tumor tissue and its microenvironment should attenuate the sympathetic neurotransmission not only temporarily but till the complete regression of the tumor tissue.

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β-Adrenergic system, a backstage manipulator regulating tumour progression and drug target in cancer therapy

Cited by 143 publications

References 111 publications

β-Adrenergic Receptors : New Target in Breast Cancer

β-Adrenergic Receptors : New Target in Breast Cancer

β-Adrenergic receptors suppress Rap1B prenylation and promote the metastatic phenotype in breast cancer cells

Sympathectomized tumor-bearing mice survive longer but develop bigger melanomas

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