ß2-Adrenoceptors on tumor cells play a critical role in stress-enhanced metastasis in a mouse model of breast cancer.
Brain Behav Immun
; 57: 106-115, 2016 Oct.
Article
en En
| MEDLINE
| ID: mdl-27321906
ABSTRACT
Chronic stress accelerates metastasis - the main cause of death in cancer patients - through the activation of ß-adrenoceptors (ßARs). We have previously shown that ß2AR 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 ßAR, the role of ß2AR signaling in tumor cells in metastasis is unclear. Therefore, to investigate the contribution of ß2AR 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 ß2AR. ß2AR 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 ß2AR in low metastatic MCF-7 breast cancer cells induced an invasive phenotype. Importantly, we found that knockdown of ß2AR in tumor cells significantly reduced the impact of stress on metastasis in vivo. These findings highlight a crucial role for ß2AR tumor cell signaling in the adverse effects of stress on metastasis, and indicate that it may be necessary to block ß2AR on tumor cells to fully control metastatic progression.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Estrés Psicológico
/
Neoplasias de la Mama
/
Receptores Adrenérgicos beta 2
/
Línea Celular Tumoral
/
Metástasis de la Neoplasia
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Brain Behav Immun
Asunto de la revista:
ALERGIA E IMUNOLOGIA
/
CEREBRO
/
PSICOFISIOLOGIA
Año:
2016
Tipo del documento:
Article
País de afiliación:
Australia