Differential β2-adrenergic receptor expression defines the phenotype of non-tumorigenic and malignant human breast cell lines

Gargiulo, Lucía; Copsel, Sabrina N.; Rivero, Ezequiel Mariano; Galès, Céline; Sénard, J M; Lüthy, Isabel Alicia; Davio, Carlos; Bruzzone, Ariana

doi:10.18632/oncotarget.2460

Cited by 33 publications

(44 citation statements)

References 45 publications

(68 reference statements)

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“…These authors have also reported that, in nontumourigenic cells, AD treatment resulted in decreased proliferation and migration rate and higher cellular adhesion, whereas, in tumour cells, the effect was opposite, i.e. AD stimulation accelerated proliferation and migration of cancer cells (26). Our results showed, for the first time, that primary melanoma cell proliferation rate is lower after AD stimulation.…”

Section: Discussionsupporting

confidence: 78%

“…As various cancers, including melanoma, are concerned, a positive correlation between the level of stress in cancer patients and progression of disease has been demonstrated (8,32). However, attempts to explain the molecular mechanisms of AD action in cancer progression (33)(34)(35) The adrenergic stimulation is suggested to accelerate cancer progression via stimulation of angiogenesis (36), regulation of MMP expression and activation (37), as well as by increased tumour cell proliferation (26). In melanoma tissues and cell lines, the expression of ADR2B has been previously reported (17,38,39).…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, our results are consistent with the observation concerning ADR2B expression in breast cancer cells. Gargiulo et al (26) have shown that the non-tumourigenic MCF-10A cells possess generally higher level of ADRB than tumour MCF-7 cells. Regarding their previously published results, they have suggested that this observation refers mainly to ADR2B.…”

Section: Discussionmentioning

confidence: 99%

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Diversified β-2-adrenergic Receptor Expression and Action in Melanoma Cells

Janik

Szlęzak

Surman

et al. 2017

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Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Diversified β-2-adrenergic Receptor Expression and Action in Melanoma Cells

Janik

Szlęzak

Surman

et al. 2017

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“…7), although this could also be attributed to nonselective cellular targets common to sotalol, timolol, and propranolol (Supplemental Table 2). MCF7 cells also express b-ARs (Supplemental Table 3; Shi et al, 2011;Işeri et al, 2014); even if the expression of the b-ARs is not as high in MCF7 cells as in other breast cancer cell lines (Vandewalle et al, 1990), radioligand binding assays have estimated that there are ∼80,000 binding sites per cell in MCF7 cells (Gargiulo et al, 2014).…”

Section: Depletion Of Er Ca 21mentioning

confidence: 99%

Differential Free Intracellular Calcium Release by Class II Antiarrhythmics in Cancer Cell Lines

Reyes-Corral

Sørensen

Thrasivoulou

et al. 2019

J Pharmacol Exp Ther

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Class II antiarrhythmics or b-blockers are antisympathetic nervous system agents that act by blocking b-adrenoceptors. Despite their common clinical use, little is known about the effects of b-blockers on free intracellular calcium (Ca 21 i), an important cytosolic second messenger and a key regulator of cell function. We investigated the role of four chemical analogs, commonly prescribed b-blockers (atenolol, metoprolol, propranolol, and sotalol), on Ca 21 i release and whole-cell currents in mammalian cancer cells (PC3 prostate cancer and MCF7 breast cancer cell lines). We discovered that only propranolol activated free Ca 21 i release with distinct kinetics, whereas atenolol, metoprolol, and sotalol did not. The propranololinduced Ca 21 i release was significantly inhibited by the chelation of extracellular calcium with ethylene glycol tetraacetic acid (EGTA) and by dantrolene, an inhibitor of the endoplasmic reticulum (ER) ryanodine receptor channels, and it was completely abolished by 2-aminoethoxydiphenyl borate, an inhibitor of the ER inositol-1,4,5-trisphosphate (IP 3) receptor channels. Exhaustion of ER stores with 4-chloro-m-cresol, a ryanodine receptor activator, or thapsigargin, a sarco/ER Ca 21 ATPase inhibitor, precluded the propranolol-induced Ca 21 i release. Finally, preincubation of cells with sotalol or timolol, nonselective blockers of b-adrenoceptors, also reduced the Ca 21 i release activated by propranolol. Our results show that different b-blockers have differential effects on whole-cell currents and free Ca 21 i release and that propranolol activates store-operated Ca 21 i release via a mechanism that involves calcium-induced calcium release and putative downstream transducers such as IP 3. The differential action of class II antiarrhythmics on Ca 21 i release may have implications on the pharmacology of these drugs.

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“…Foi observado também, que o estímulo de receptores adrenérgicos, pela a norepinefrina e/ou a epinefrina, regula diretamente as funções das células neoplásicas (ANTONI et al, 2006;THAKER et al, 2006;LIU et al, 2008a;LIU et al, 2008b;YANG et al, 2009;BERNABÉ et al, 2011;PARK et al, 2011;TOLL et al, 2011;PEREZ PIÑERO et al, 2012;GARGIULO et al, 2014;WNOROWSKI et al, 2015 (MASUR et al, 2001;THAKER et al, 2006;LIU et al, 2008a;LIU et al, 2008b;SHANG;LIU;LIANG, 2009;SIVAMANI et al, 2009;YANG et al, 2009;BERNABÉ et al, 2011;BRAVO-CALDERÓN et al, 2011;MADDEN;SZPUNAR;BROWN, 2011;PARK et al, 2011;STEENHUIS et al, 2011;TOLL et al, 2011;COLE;SOOD, 2012;PEREZ PIÑERO et al, 2012;GARGIULO et al, 2014;WANG et al, 2015;WNOROWSKI et al, 2015 (MASUR et al, 2001;SOOD et al, 2006;YANG et al, 2006;YU et al, 2007;SHANG;LIU;LIANG, 2009;MORETTI ...…”

Section: Sunclassified

Migração e invasão do câncer de boca via ativação de receptor beta 2 adrenérgico por mediador do estresse

Calderón¹

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Ao Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), pelo apoio financeiro sob a forma de bolsa de doutorado (Processo #142790/2011-7). À Fundação de Apoio à Pesquisa do Estado de São Paulo (FAPESP), pelo apoio financeiro na forma de Auxilio Regular à Pesquisa (Processo #2010/06333-3). Muito Obrigado! RESUMO A ativação do receptor beta 2 adrenérgico (β2-AR), pelos mediadores químicos do estresse, pode induzir efeitos estimuladores ou inibidores na migração e invasão celular, dependendo do tipo de tumor maligno. A importância deste receptor na evolução do câncer de boca não está totalmente esclarecida. O objetivo deste estudo foi verificar a expressão do β2-AR em linhagens de carcinomas espinocelular de boca (SCC-9 e SCC-25), e investigar o papel da ativação deste receptor pela norepinefrina e de seu bloqueio por um antagonista na migração e invasão destas células neoplásicas. As células SCC-9 e SCC-25 foram investigadas quanto à expressão gênica e proteica do β2-AR, respectivamente, pelo RT-qPCR e pelo Western blot. A migração e a invasão celular foram analisadas pelo ensaio de cicatrização de feridas e pelo sistema de câmeras de invasão Transwell, respectivamente. Diferentes concentrações (0,1; 1 e 10µM) de norepinefrina foram utilizadas para estimular e 1µM de propranolol foi empregado para bloquear os receptores beta adrenérgicos nas células neoplásicas. As diferenças das médias obtidas nos experimentos de invasão e migração de SCC-9 e SCC-25 e da expressão proteica do β2-AR, foram comparadas pelo teste t de Student com nível de significância de 5%. Os resultados mostraram que a expressão gênica e proteica do β2-AR foi verificada em ambas as linhagens de câncer de boca. A concentração de 10µM de norepinefrina inibiu, significativamente (p≤0,05), a migração e invasão celular de SCC-9 e SCC-25, sendo este efeito mais acentuado nas células SCC-25. Além disso, houve uma redução significativa (p≤0,05) do efeito da norepinefrina na migração celular quando os β2-AR foram inibidos pelo propranolol. Adicionalmente, o bloqueio dos β-ARs pelo propranolol reverteu parcialmente o efeito da norepinefrina na capacidade invasiva de SCC-9 e SCC-25. Estes resultados comprovam que a norepinefrina, via ativação do β2-AR, reduziu a migração e a invasão das células do carcinoma espinocelular de boca e, portanto, o uso de agonistas dos receptores beta-adrenérgicos poderia se tornar um alvo terapêutico adjuvante no tratamento desta neoplasia maligna. Palavras-chave: Câncer de boca. Estresse. Receptor beta 2 adrenérgico.

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Differential β2-adrenergic receptor expression defines the phenotype of non-tumorigenic and malignant human breast cell lines

Cited by 33 publications

References 45 publications

Diversified β-2-adrenergic Receptor Expression and Action in Melanoma Cells

Diversified β-2-adrenergic Receptor Expression and Action in Melanoma Cells

Differential Free Intracellular Calcium Release by Class II Antiarrhythmics in Cancer Cell Lines

Migração e invasão do câncer de boca via ativação de receptor beta 2 adrenérgico por mediador do estresse

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