Abstract
Metastasis to the liver is a main factor in colorectal cancer mortality. Previous studies suggest that chronic psychological stress is important in cancer progression, but its effect on liver metastasis has not been investigated. To address this, we established a liver metastasis model in BALB/c nude mice to investigate the role of chronic stress in liver metastasis. Our data suggest that chronic stress elevates catecholamine levels and promotes liver metastasis. Chronic stress was also associated with increased tumor associated macrophages infiltration into the primary tumor and increased the expression of metastatic genes. Interestingly, β-blocker treatment reversed the effects of chronic stress on liver metastasis. Our results suggest the β-adrenergic signaling pathway is involved in regulating colorectal cancer progression and liver metastasis. Additionally, we submit that adjunctive therapy with a β-blocker may complement existing colorectal cancer therapies.
Highlights
Data Availability Statement: All relevant data are within the paper
To investigate the role of chronic stress on primary tumor growth and liver metastasis, we evaluated the weights of spleen and liver
We found that chronic stress increased the growth and metastasis of colorectal cancer (CRC) through β-adrenergic signaling (Fig 7)
Summary
As cancer diagnosis can cause major distress, patients often experience fear, anxiety, and depression [9] These signals can activate stress pathways, including the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system (SNS), and elicit. Effect of Chronic Stress on Liver Metastasis physiological responses These pathways may produce neurotransmitters and hormones that alter the tumor microenvironment. Previous studies suggest that stress hormones-induced CRC cell proliferation is adrenoreceptor dependent and that chronic stress could promote the tumor growth of subcutaneously implanted colon carcinoma cells in a nude mice model through the β-AR signaling pathway [15, 16]. We investigate how chronic stress affects liver metastasis using an in vivo metastatic model of colon cancer, and determine whether the β-AR signaling pathway is required for the progression of CRC
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