Norepinephrine Promotes the beta 1-Integrin-Mediated Adhesion of MDA-MB-231 Cells to Vascular Endothelium by the Induction of a GRO alpha Release

作者：Strell Carina; Niggemann Bernd; Voss Melanie J; Powe Desmond G; Zaenker Kurt S; Entschladen Frank^*

来源：Molecular Cancer Research, 2012, 10(2): 197-207.

DOI：10.1158/1541-7786.MCR-11-0130

The migratory activity of tumor cells and their ability to extravasate from the blood stream through the vascular endothelium are important steps within the metastasis cascade. We have shown previously that norepinephrine is a potent inducer of the migration of MDA-MB-468 human breast carcinoma cells and therefore investigated herein, whether the interaction of these cells as well as MDA-MB-231 and MDA-MB-435S human breast carcinoma cells with the vascular endothelium is affected by this neurotransmitter as well. By means of a flow-through assay under physiologic flow conditions, we show that norepinephrine induces an increase of the adhesion of the MDA-MB-231 cells, but not of MDA-MB-468 and MDA-MB-435S cells to human pulmonary microvascular endothelial cells (HMVEC). The adhesion of MDA-MB-231 cells was based on a norepinephrine-mediated release of GRO alpha from HMVECs. GRO alpha caused a beta 1-integrin-mediated increase of the adhesion of MDA-MB-231 cells. Most interestingly, this effect of norepinephrine, similar to the aforementioned induction of migration in MDA-MB-468 cells, was mediated by beta-adrenergic receptors and therefore abrogated by beta-blockers. In conclusion, norepinephrine has cell line-specific effects with regard to certain steps of the metastasis cascade, which are conjointly inhibited by clinically established beta-blockers. Therefore, these results may deliver a molecular explanation for our recently published retrospective data analysis of patients with breast cancer which shows that beta-blockers significantly reduce the development of metastases. Mol Cancer Res; 10(2); 197-207.

• 出版日期2012-2