β2-Adrenoceptors on tumor cells play a critical role in stress-enhanced metastasis in a mouse model of breast cancer

Chang, Aeson; Le, Caroline P.; Walker, Adam K.; Creed, Sarah J.; Pon, Cindy K.; Albold, Sabine; Carroll, Dominic; Halls, Michelle L.; Lane, J. Robert; Riedel, Bernhard; Ferrari, Davide; Sloan, Erica K.

Abstract

© 2016 The Authors Chronic stress accelerates metastasis – the main cause of death in cancer patients – through the activation of β-adrenoceptors (βARs). We have previously shown that β2AR signaling in MDA-MB-231HM breast cancer cells, facilitates invadopodia formation and invasion in vitro. However, in the tumor microenvironment where many stromal cells also express βAR, the role of β2AR signaling in tumor cells in metastasis is unclear. Therefore, to investigate the contribution of β2AR signaling in tumor cells to metastasis in vivo, we used RNA interference to generate MDA-MB-231HM breast cancer cells that are deficient in β2AR. β2AR knockdown in tumor cells reduced the proportion of cells with a mesenchymal-like morphology and, as expected, reduced tumor cell invasion in vitro. Conversely, overexpression of β2AR in low metastatic MCF-7 breast cancer cells induced an invasive phenotype. Importantly, we found that knockdown of β2AR in tumor cells significantly reduced the impact of stress on metastasis in vivo. These findings highlight a crucial role for β2AR tumor cell signaling in the adverse effects of stress on metastasis, and indicate that it may be necessary to block β2AR on tumor cells to fully control metastatic progression.

Citation

Chang, A., Le, C. P., Walker, A. K., Creed, S. J., Pon, C. K., Albold, S., …Sloan, E. K. (2016). β2-Adrenoceptors on tumor cells play a critical role in stress-enhanced metastasis in a mouse model of breast cancer. Brain, Behavior, and Immunity, 57, 106-115. https://doi.org/10.1016/j.bbi.2016.06.011

• Journal Article Type: Article
• Acceptance Date: Jun 15, 2016
• Online Publication Date: Jun 16, 2016
• Publication Date: 2016-10
• Deposit Date: Feb 27, 2020
• Publicly Available Date: Feb 27, 2020
• Journal: Brain, Behavior, and Immunity
• Print ISSN: 0889-1591
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 57
• Pages: 106-115
• DOI: https://doi.org/10.1016/j.bbi.2016.06.011
• Public URL: https://nottingham-repository.worktribe.com/output/4045939
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S0889159116301908
• Additional Information: This article is maintained by: Elsevier; Article Title: β2-Adrenoceptors on tumor cells play a critical role in stress-enhanced metastasis in a mouse model of breast cancer; Journal Title: Brain, Behavior, and Immunity; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.bbi.2016.06.011; Content Type: article; Copyright: © 2016 The Authors. Published by Elsevier Inc.