Chronic restraint stress promotes hepatocellular carcinoma growth by mobilizing splenic myeloid cells through activating β-adrenergic signaling

Jiang, Wei; Yu, Li; Li, Zhenzhen; Sun, Jin; Li, Jiangwei; Wei, Wei; Li, Liang; Zhang, Chen; Huang, Chen; Yang, Shifeng; Yang, Jun; Kong, Guangyao; Li, Zong-Fang

doi:10.1016/j.bbi.2019.05.031

Cited by 43 publications

(29 citation statements)

References 44 publications

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“…More recently, a study has reported that chronic stress promotes HCC growth by redistributing splenic myeloid cells to tumor tissues. 16 In our study, we observe a significant increase in the percentage of Recently, CXCL5 has been the focus of studies examining the role of chemokines in carcinogenesis and tumor progression. CXCL5 is overexpressed in various cancers including liver, prostate and pancreatic cancers.…”

Section: Discussionsupporting

confidence: 54%

“…38 It has also been reported that CXCR2 mediates the mobilization of splenic myeloid cells in tumor-bearing mice. 16 In our study, we demonstrate that the Although we demonstrate that β-adrenergic signaling contributes to MDSCs mobilization under chronic stress, the specific receptor subtype remains unclear. Three classes of β-ARs have been identified as β1, β2 and β3.…”

Section: Discussionmentioning

confidence: 57%

“…Hematoxylin and eosin (H&E) staining was performed as described previously. 16 Briefly, the sections from control (n = 7) and stress group (n = 8) were deparaffinized through xylene and alcohol gradients, rehydrated to water, stained with hematoxylin for 8 minutes, washed with distilled water for 3 minutes, differentiated in 1% acid alcohol and rinsed in tap water. Next, the tissue sections were stained with eosin for 1 minute, dehydrated and mounted in neutral resin.…”

Section: Tissue Preparation and Histological Stainingmentioning

confidence: 99%

“…13,14 Recent researches indicate that β-AR contributes to the regulation of immunosuppressive potential and the recruitment of MDSCs. 15,16 Thus, it is obscure that which GR or AR plays a dominant role in mobilization and function regulation of MDSCs in tumor-bearing mice exposed to psychological stress. Meanwhile, the role of signaling pathway in bone marrow MDSCs (BM-MDSCs) under psychological stress remains entirely unknown.…”

Section: Introductionmentioning

confidence: 99%

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Chronic restraint stress promotes the mobilization and recruitment of myeloid‐derived suppressor cells through β‐adrenergic‐activated CXCL5‐CXCR2‐Erk signaling cascades

Cao

Huang

Chen

et al. 2021

Intl Journal of Cancer

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Myeloid-derived suppressor cells (MDSCs) play an important role in tumor immune escape. Recent studies have shown that MDSCs contribute to tumor progression under psychological stress, but the underlying mechanism of MDSCs mobilization and recruitment remains largely unknown. In the present study, a chronic restraint stress paradigm was applied to the H22 hepatocellular carcinoma (HCC) bearing mice to mimic the psychological stress. We observed that chronic restraint stress significantly promoted HCC growth, as well as the mobilization of MDSCs to spleen and tumor sites from bone marrow. Meanwhile, chronic restraint stress enhanced the expression of C-X-C motif chemokine receptor 2 (CXCR2) and pErk1/2 in bone marrow MDSCs, together with elevated chemokine (C-X-C motif) ligand 5 (CXCL5) expression in tumor tissues. In vitro, the treatments of MDSCs with epinephrine (EPI) and norepinephrine (NE) but not corticosterone (CORT)-treated H22 conditioned medium obviously inhibited T-cell proliferation, as well as enhanced CXCR2 expression and extracellular signal-regulated kinase (Erk) phosphorylation. In vivo, β-adrenergic blockade with propranolol almost completely reversed the accelerated tumor growth induced by chronic restraint stress and inactivated CXCL5-CXCR2-Erk signaling pathway. Our findings support the crucial role of β-adrenergic signaling cascade in the mobilization and recruitment of MDSCs under chronic restraint stress.

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Section: Discussionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 57%

Section: Tissue Preparation and Histological Stainingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Chronic restraint stress promotes the mobilization and recruitment of myeloid‐derived suppressor cells through β‐adrenergic‐activated CXCL5‐CXCR2‐Erk signaling cascades

Cao

Huang

Chen

et al. 2021

Intl Journal of Cancer

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“…Stress response is a complex process, in which environmental factors and mental factors are involved to modulate the immune system by activating nervous system [7] , [24] . Previous studies showed that psychological stress regulates immune response and influences the redistribution of leukocytes through stress responses by activating the sympathetic nervous system (SNS) and hypothalamus–pituitary-adrenal cortex (HPA) axis, which release catecholaminergic neurotransmitters and corticosterone [6] , [8] , [9] , [13] . Thus, the changes of immune cells of the frontline medical workers may be caused by psychological stress.…”

Section: Discussionmentioning

confidence: 99%

Immune response of frontline medical workers providing medical support for Wuhan COVID-19 patients, China

Yang

Wang

Zhang

et al. 2021

International Immunopharmacology

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The outbreak of novel coronavirus disease 2019 (COVID-19) posed a great challenge and stress to frontline medical workers in China. Stress is closely related to immunity. However, the immune response of frontline medical workers providing medical support for COVID-19 patients is unclear. Here, we reported the immune response of 76 frontline medical workers and 152 controls from the Second Affiliated Hospital of Xi’an Jiaotong University. The frontline medical workers were involved in the care for Wuhan COVID-19 patients from February 8 to March 31, 2020 in Tongji Hospital of Huazhong University of Science and Technology. The controls were medical workers of our hospital who had not been in contact with COVID-19 patients during the same period. Demographic and clinical data, including routine blood test data were extracted from the electronic health examination record and retrospectively analyzed. The post-stress frontline medical workers had higher lymphocyte (LYM) count compared with controls or pre-stress. However, the post-stress frontline medical workers had lower monocyte (MONO) count, neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR) and neutrophil (NEUT) ratio than controls or pre-stress. Interestingly, we found the differences were more significantly in female subgroup and nurse subgroup. Together, these data indicated that changes of immune response were found in frontline medical workers providing medical support for Wuhan COVID-19 patients, especially in females and nurses. Those maybe caused by psychological stress and we recommend to pay more attention to mental health of frontline medical workers, and provide appropriate psychological interventions for them.

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Hepatocellular Carcinoma

Mravec

2024

Neurobiology of Cancer

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Chronic restraint stress promotes hepatocellular carcinoma growth by mobilizing splenic myeloid cells through activating β-adrenergic signaling

Cited by 43 publications

References 44 publications

Chronic restraint stress promotes the mobilization and recruitment of myeloid‐derived suppressor cells through β‐adrenergic‐activated CXCL5‐CXCR2‐Erk signaling cascades

Chronic restraint stress promotes the mobilization and recruitment of myeloid‐derived suppressor cells through β‐adrenergic‐activated CXCL5‐CXCR2‐Erk signaling cascades

Immune response of frontline medical workers providing medical support for Wuhan COVID-19 patients, China

Hepatocellular Carcinoma

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