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

ABSTRACT: Chronic stress accelerates metastasis - the main cause of death in cancer patients - through the activation of ?-adrenoceptors (?ARs). We have previously shown that ?2AR 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 ?AR, the role of ?2AR signaling in tumor cells in metastasis is unclear. Therefore, to investigate the contribution of ?2AR 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 ?2AR. ?2AR 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 ?2AR in low metastatic MCF-7 breast cancer cells induced an invasive phenotype. Importantly, we found that knockdown of ?2AR in tumor cells significantly reduced the impact of stress on metastasis in vivo. These findings highlight a crucial role for ?2AR tumor cell signaling in the adverse effects of stress on metastasis, and indicate that it may be necessary to block ?2AR on tumor cells to fully control metastatic progression.

SUBMITTER: Chang A 

PROVIDER: S-EPMC5060133 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature