Beta adrenergic receptor activation inhibits oral cancer migration and invasiveness

Bravo-Calderón, Diego Mauricio; Assáo, Agnes; Garcia, Natália Galvão; Coutinho‐Camillo, Cláudia Malheiros; Roffé, Martín; Germano, Janaina Naiara; Oliveira, Denise Tostes

doi:10.1016/j.archoralbio.2020.104865

Cited by 19 publications

(9 citation statements)

References 24 publications

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“…While some in vitro studies have shown that the activation of the beta-adrenergic pathway seems to be implicated in increased proliferative activity [14] , invasion, and EMT [15] of head and neck cancer cells, other studies have had opposing findings. The stimulation of HNSCC cells with agonists of the beta-adrenergic receptors has resulted in decrease in HNSCC cell migration, invasion [ 16 , 17 ], and EMT [18] . Clinical studies have obtained dissonant findings as well.…”

Section: Introductionmentioning

confidence: 99%

Beta-adrenergic pathway activation enhances aggressiveness and inhibits stemness in head and neck cancer

Lopes-Santos

Bernabé

Miyahara

et al. 2021

Translational Oncology

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Highlights ADRB2 high /SLC6A2 high tumors presented enhanced aggressiveness ADRB2 high /SLC6A2 high tumors had cell stemness inhibited Fifty-six drugs were identified as potential targets for personalized treatment

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Section: Introductionmentioning

confidence: 99%

Beta-adrenergic pathway activation enhances aggressiveness and inhibits stemness in head and neck cancer

Lopes-Santos

Bernabé

Miyahara

et al. 2021

Translational Oncology

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“…On the contrary, numerous studies concluded distinct results in terms of the β2-AR signals. Bravo-Calderón et al ( 22 ) showed that 10 µM of norepinephrine (a β2-AR agonist) significantly inhibited the migration of SCC-9 and SCC-25 oral squamous cell carcinoma cell lines while a significant reversion was observed by using β2-AR antagonist propranolol. Baker et al ( 52 ) found that acute systemic β-AR activation in healthy donors markedly augmented the mobilization, expansion, and anti-tumor activity of T γδ cells.…”

Section: Discussionmentioning

confidence: 99%

“…Zahalka et al showed that the loss of endothelial ADRB2 weaken angiogenesis in prostate cancer (20). However, other reports also indicated that β2-AR activation significantly suppressed tumor growth (15,(21)(22)(23)(24). Sakakitani et al (24) demonstrated that β2-AR agonist inhibited cell motility and induced mesenchymal-epithelial transition in oral cancer.…”

Section: Introductionmentioning

confidence: 99%

ADRB2 is a potential protective gene in breast cancer by regulating tumor immune microenvironment

Wei¹,

Chen²,

Yang³

et al. 2021

Transl Cancer Res TCR

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Background: Breast cancer (BRCA) is the leading cause of cancer death among females. Studies suggested that β-adrenoceptors involved in tumor progression by regulating immune system. However, how ADRB2 affects the immune infiltration in BRCA is still being unraveled.Methods: Expressions of ADRB2 in multiple tissues, cancers and blood cells were analyzed by using the Human Protein Atlas and UALCAN database. Expression differentiation of ADRB2 in tumor microenvironment (TME) of BRCA was detected in TISCH database. Correlations between ADRB2 and immune cell infiltration were analyzed by TIMER 2.0, and co-expression genes of ADRB2 were obtained from the cBioPortal website. Functional enrichment analyses and protein-protein interactions were constructed as well. Finally, the potential mechanisms of ADRB2 and candidate drugs targeting BRCA were discussed by using the Metascape, STITCH and Cmap tools.Results: ADRB2 was significantly down-regulated in BRCA, and lower ADRB2 expression often resulted in worse prognosis in BRCA patients. ADRB2 was mainly expressed in breast tissue and blood. Among blood cell subtypes and TME of BRCA, ADRB2 was specifically expressed in T cell subtypes. Also, ADRB2 expression level was positively correlated with the infiltration levels of immune cells such as CD4+ T cell, CD8+ T cell, Tγδ and myeloid DC while negatively correlated with Treg, Tfh and myeloid-derived suppressor cell. Furthermore, functional enrichment analyses revealed that most enriched pathways were immune-related, especially in T cell-related pathways. Also, transcription factors (TFs) analyses showed that most downstream TFs regulated by ADRB2 were immune-related, and most candidate drugs had promising anti-tumor effects.Conclusions: In conclusion, ADRB2 was a potential protective gene in BRCA, and it might play a vital role in regulating immune responses. The expression level of ADRB2 was positively correlated with immune cells infiltration in BRCA, especially for T cells. Therefore, ADRB2 would be a target for boosting immunotherapy effects in BRCA.

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“…Propranolol competitively inhibits the action of epinephrine and norepinephrine on β1-and β2-ARs (46). Multiple studies have shown that propranolol inhibits expression of β2-AR (47,48). Previously, the effect of propranolol on bone metabolism has received attention (41,49,50).…”

Section: Discussionmentioning

confidence: 99%

Effect and mechanism of propranolol on promoting osteogenic differentiation and early implant osseointegration

et al. 2021

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The present study aimed to investigate the effect of β-receptor blocker propranolol on early osseointegration of pure titanium implants and the underlying molecular regulatory mechanisms. An implant osseointegration model using the tibial metaphysis of New Zealand rabbits was established. The rabbits were divided into control and low-, medium-and high-dose propranolol groups. The formation of implant osseointegration was detected by X-ray scanning. Mesenchymal stem cells (MScs) and osteoblasts (OBs) were isolated and cultured in vitro, isoproterenol was supplemented to simulate sympathetic action and propranolol was subsequently administrated. The effect of propranolol on cell proliferation and osteogenic differentiation were assessed by EdU, flow cytometry, alizarin red staining and alkaline phosphatase (ALP) detection. The expression levels of bone morphogenetic protein (BMP)2, RUNX family transcription factor (RunX)2, collagen (cOL)-1, osteocalcin (OcN) and β2-adrenergic receptor (AR) were detected by immunofluorescence, reverse transcription-quantitative PcR and western blot assay. Propranolol effectively promoted implant osseointegration in vivo, facilitated proliferation of OBs, inhibited proliferation of MScs and enhanced osteogenic differentiation of OBs and MScs. The calcium content and ALP activity of cells treated with propranolol were markedly higher than in the control group. Propranolol also elevated mRNA and protein expression levels of BMP2, RunX2, cOL-1 and OcN in tissue and cells, and decreased the expression of β2-AR. The present study demonstrated that the β-receptor blocker propranolol promoted osteogenic differentiation of OBs and MScs and enhanced implant osseointegration. The present study provided a novel insight into the application and regulatory mechanisms of propranolol.

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Beta adrenergic receptor activation inhibits oral cancer migration and invasiveness

Cited by 19 publications

References 24 publications

Beta-adrenergic pathway activation enhances aggressiveness and inhibits stemness in head and neck cancer

Beta-adrenergic pathway activation enhances aggressiveness and inhibits stemness in head and neck cancer

ADRB2 is a potential protective gene in breast cancer by regulating tumor immune microenvironment

Effect and mechanism of propranolol on promoting osteogenic differentiation and early implant osseointegration

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