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20. ß2-Adrenergic agonist treatment inhibits 4T1 breast tumor metastasis to the lung

Brain Behavior and Immunity
DOI: 10.1016/j.bbi.2014.06.040
  • Biology


Solid tumors are composed of neoplastic cells and non-cancerous stromal cells consisting of immune cells, fibroblasts, and endothelial cells. To determine how ß2-adrenergic receptor (ß2-AR) activation of stromal cells influences cancer progression in the absence of tumor cell ß2-AR activation, we utilized the mammary adenocarcinoma 4T1, a murine model of metastatic breast cancer. 4T1 cells do not express functional ß-AR and are unable to respond to ß-AR agonists or the endogenous ß-AR ligand, norepinephrine. BALB/c female mice were injected IP with 5mg/kg salmeterol, a long-acting ß2-AR-selective agonist, or saline beginning 2days before tumor cell injection and continued daily until 24h before sacrifice. In BALB/c mice, salmeterol treatment significantly reduced metastasis to the lungs in association with decreased tumor myeloid derived suppressor cells (CD11b+Gr-1+) and a non-significant reduction in tumor growth. To test if the inhibitory effects of salmeterol were dependent on T cell function, BALB/c SCID mice were treated with salmeterol. In the absence of mature T cells, salmeterol treatment did not reduce lung metastases or tumor growth. These results provide evidence that ß2-AR activation can inhibit tumor growth and metastasis through host ß2-AR-expressing stromal cells including T cells and myeloid derived suppressor cells. Targeting stromal cell ß2-AR may inhibit metastasis in the context of aggressive breast cancer.

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