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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

Authors

Aeson Chang

Caroline P Le

Adam K Walker

Sarah J Creed

Cindy K Pon

Sabine Albold

Dominic Carroll

Michelle L Halls

ROB LANE ROB.LANE@NOTTINGHAM.AC.UK
Associate Professor

Bernhard Riedel

Davide Ferrari

Erica K Sloan



Abstract

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-231(HM) 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-231(HM) 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.

Journal Article Type Article
Publication Date 2016-10
Journal Brain, Behavior, and Immunity
Print ISSN 0889-1591
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 57
Pages 106-115
APA6 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
DOI https://doi.org/10.1016/j.bbi.2016.06.011
Publisher URL https://www.sciencedirect.com/science/article/pii/S0889159116301908

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