Chewing Behavior Attenuates Lung-Metastasis-Promoting Effects of Chronic Stress in Breast-Cancer Lung-Metastasis Model Mice

SIMPLE SUMMARY: Breast-cancer-related death is mainly caused by distal metastasis. One of the most common metastatic sites for breast cancer is the lung. In the mouse model of breast-cancer lung metastasis, we showed that chronic psychological stress accelerated the lung metastasis of breast cancer by increasing the level of stress hormones and their receptors, oxidative stress, and the subsequent signaling-molecules involving angiogenesis and matrix degradation. Chewing, or active mastication, is a practical behavior for coping with psychological stress effectively. We identified the fact that chewing behavior could relieve chronic stress and ameliorate the promoting effects of chronic psychological-stress on the lung metastasis of breast cancer, via modulating stress-hormones and their receptors, and the downstream signaling-pathways. ABSTRACT: We assessed the effects of chewing behavior on the lung-metastasis-promoting impact of chronic psychological-stress in mice. Human breast-cancer cells (MDA-MB-231) were injected into the tail vein of female nude mice. Mice were randomly divided into stress, stress-with-chewing, and control groups. We created chronic stress by placing mice in small transparent tubes for 45 min, 3 times a day for 7 weeks. Mice in the stress-with-chewing group were allowed to chew wooden sticks during the experimental period. The histopathological examination showed that chronic psychological-stress increased lung metastasis, and chewing behavior attenuated the stress-related lung metastasis of breast-cancer cells. Chewing behavior decreased the elevated level of the serum corticosterone, normalized the increased expression of glucocorticoid, and attenuated the elevated expression of adrenergic receptors in lung tissues. We also found that chewing behavior normalized the elevated expression of inducible nitric oxide synthase, 4-hydroxynonenal, and superoxide dismutase 2 in lung tissues, induced by chronic stress. The present study demonstrated that chewing behavior could attenuate the promoting effects of chronic psychological-stress on the lung metastasis of breast-cancer cells, by regulating stress hormones and their receptors, and the downstream signaling-molecules, involving angiogenesis and oxidative stress.