Inhibition of β2-adrenergic receptor reduces triple-negative breast cancer brain metastases: The potential benefit of perioperative β-blockade.
Inhibition of β2-adrenergic receptor reduces triple-negative breast cancer brain metastases: The potential benefit of perioperative β-blockade.
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DOI：
10.3892/or.2016.4710
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发表时间：
2016-06
期刊：
影响因子：
4.2
通讯作者：
Lew MW
中科院分区：
文献类型：
--
作者：
Choy C;Raytis JL;Smith DD;Duenas M;Neman J;Jandial R;Lew MW
作为对最近研究的回应，我们调查了围手术期β阻断与乳腺癌转移之间的关系。首先，对2000年至2010年间在希望之城癌症中心接受乳腺癌手术的1,029名患者进行了一项回顾性研究，调查围手术期β阻滞剂的使用与癌症复发和转移的关系。我们跟踪临床研究，检测原代和脑转移乳腺癌细胞对β-2激活和抑制的体外增殖、迁移和侵袭。我们还在体内研究了心得安处理的转移细胞的转移潜能。对于II期乳腺癌患者，经COX回归分析，围手术期β阻断与降低肿瘤复发有关(危险比=0.51；95%可信区间：0.23-0.97；p=0.041)。三阴性(TN)脑转移细胞相对于TN原代细胞β-2-肾上腺素能受体基因和蛋白表达增加。作为对β2-肾上腺素能受体激活的反应，TN脑转移细胞也表现出与对照组相比细胞增殖和迁移的增加。这些作用可被普萘洛尔消除。心得安可降低β-2肾上腺素能受体激活的侵袭力。在体内，普萘洛尔处理TN脑转移细胞可减少脑转移的建立。我们的结果提示，应激和相应的β-2激活可能促进了TN乳腺癌细胞脑转移的建立。此外，我们的数据表明，在乳腺癌复发和转移方面，围手术期阻断β对乳腺癌复发和转移有好处。
In response to recent studies, we investigated an association between perioperative β-blockade and breast cancer metastases. First, a retrospective study examining perioperative β-blocker use and cancer recurrence and metastases was conducted on 1,029 patients who underwent breast cancer surgery at the City of Hope Cancer Center between 2000 and 2010. We followed the clinical study and examined proliferation, migration, and invasion in vitro of primary and brain-metastatic breast cancer cells in response to β2-activation and inhibition. We also investigated in vivo the metastatic potential of propranolol-treated metastatic cells. For stage II breast cancer patients, perioperative β-blockade was associated with decreased cancer recurrence using Cox regression analysis (hazard's ratio =0.51; 95% CI: 0.23–0.97; p=0.041). Triple-negative (TN) brain-metastatic cells were found to have increased β2-adrenergic receptor mRNA and protein expression relative to TN primary cells. In response to β2-adrenergic receptor activation, TN brain-metastatic cells also exhibited increased cell proliferation and migration relative to the control. These effects were abrogated by propranolol. Propranolol decreased β2-adrenergic receptor-activated invasion. In vivo, propranolol treatment of TN brain-metastatic cells decreased establishment of brain metastases. Our results suggest that stress and corresponding β2-activation may promote the establishment of brain metastases of TN breast cancer cells. In addition, our data suggest a benefit to perioperative β-blockade during surgery-induced stress with respect to breast cancer recurrence and metastases.