Brain metastases of mouse mammary adenocarcinoma is increased by acute stress

Brain metastases from mammary adenocarcinoma constitute the chief cause of morbidity and mortality. Some evidence suggests that stress may contribute to disease progression and metastases. Here we show that acute restraint stress (30 min) induces statistically significant increase in brain metastases of systemically administered luciferase-tagged 4T1-BR-3P mouse mammary adenocarcinoma cells as evidenced by the total brain-associated photons from 5.6 × 10⁷ photons in unstressed controls to 1.7 × 10 ⁸ photons in C57BL/6 (p = 0.0018) and from 7.6 × 10⁷ to 2.1 × 10⁷ photons in BALB/c (p = 0.004) mice. Acute stress may increase metastases by disrupting the blood-brain-barrier (BBB), through release of corticotropin-releasing-hormone (CRH) activating perivascular brain mast cells.