Chronic stress promotes breast carcinoma metastasis by accumulating myeloid-derived suppressor cells through activating β-adrenergic signaling

Numerous studies have found that chronic stress could promote tumor progression and this may be related to inhibtion of immune system. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells with immunosuppressive activity. MDSCs may represent a key link between chronic stre...

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Autores principales:	Jiale an, Lifeng Feng, Jiling Ren, Yafei Li, Guangru Li, Chang Liu, Yong Yao, Ye Yao, Zecheng Jiang, Yang Gao, Yang Xu, Yachen Wang, Jing Li, Jie Liu, Lei Cao, Zhi Qi, Liang Yang
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2021
Materias:	chronic stress mdscs il-6/stat3 Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/17bd0be37f2145998c84f2ad46b4db48
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spelling	oai:doaj.org-article:17bd0be37f2145998c84f2ad46b4db482021-11-26T11:19:49ZChronic stress promotes breast carcinoma metastasis by accumulating myeloid-derived suppressor cells through activating β-adrenergic signaling2162-402X10.1080/2162402X.2021.2004659https://doaj.org/article/17bd0be37f2145998c84f2ad46b4db482021-01-01T00:00:00Zhttp://dx.doi.org/10.1080/2162402X.2021.2004659https://doaj.org/toc/2162-402XNumerous studies have found that chronic stress could promote tumor progression and this may be related to inhibtion of immune system. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells with immunosuppressive activity. MDSCs may represent a key link between chronic stress and tumor progression. However, the role of stress-induced MDSCs in breast cancer progression is unclear. The present study showed that pre-exposure of chronic stress could lead to MDSCs elevation and facilitated breast cancer metastasis in tumor-bearing mice. Adoptive transfer of MDSCs could significantly increase lung metastatic foci. In contrast, lung metastasis could be alleviated by depleting endogenous MDSCs with Gr-1 antibody. The concentration of norepinephrine in serum and the expression of tyrosine hydroxylase in bone marrow could be significantly elevated by chronic stress. Moreover, propranolol, an inhibitor of β-adrenergic signaling, could inhibit breast carcinoma metastasis and prevent the expansion of chronic stress-induced MDSCs. Further study revealed that the expressions of IL-6 and JAK/STAT3 signaling pathways were upregulated by chronic stress in mice, and this upregulation could be inhibited by propranolol. Blocking the IL-6 signal or inhibiting the activation of the JAK/STAT3 signaling pathway could reduce tumor growth and metastasis by attenuating the accumulation of MDSCs in vivo. Besides, propranolol inhibited the expression of IL-6 in supernatant of 4T1 cells induced by isoproterenol and reduced the proportion of inducible MDSCs in vitro. Taken together, these data indicated that chronic stress may accumulate MDSCs via activation of β-adrenergic signaling and IL-6/STAT3 pathway, thereby promoting breast carcinoma metastasis.Jiale anLifeng FengJiling RenYafei LiGuangru LiChang LiuYong YaoYe YaoZecheng JiangYang GaoYang XuYachen WangJing LiJie LiuLei CaoZhi QiLiang YangTaylor & Francis Grouparticlechronic stressmdscsil-6/stat3Immunologic diseases. AllergyRC581-607Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENOncoImmunology, Vol 10, Iss 1 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	chronic stress mdscs il-6/stat3 Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	chronic stress mdscs il-6/stat3 Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Jiale an Lifeng Feng Jiling Ren Yafei Li Guangru Li Chang Liu Yong Yao Ye Yao Zecheng Jiang Yang Gao Yang Xu Yachen Wang Jing Li Jie Liu Lei Cao Zhi Qi Liang Yang Chronic stress promotes breast carcinoma metastasis by accumulating myeloid-derived suppressor cells through activating β-adrenergic signaling
description	Numerous studies have found that chronic stress could promote tumor progression and this may be related to inhibtion of immune system. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells with immunosuppressive activity. MDSCs may represent a key link between chronic stress and tumor progression. However, the role of stress-induced MDSCs in breast cancer progression is unclear. The present study showed that pre-exposure of chronic stress could lead to MDSCs elevation and facilitated breast cancer metastasis in tumor-bearing mice. Adoptive transfer of MDSCs could significantly increase lung metastatic foci. In contrast, lung metastasis could be alleviated by depleting endogenous MDSCs with Gr-1 antibody. The concentration of norepinephrine in serum and the expression of tyrosine hydroxylase in bone marrow could be significantly elevated by chronic stress. Moreover, propranolol, an inhibitor of β-adrenergic signaling, could inhibit breast carcinoma metastasis and prevent the expansion of chronic stress-induced MDSCs. Further study revealed that the expressions of IL-6 and JAK/STAT3 signaling pathways were upregulated by chronic stress in mice, and this upregulation could be inhibited by propranolol. Blocking the IL-6 signal or inhibiting the activation of the JAK/STAT3 signaling pathway could reduce tumor growth and metastasis by attenuating the accumulation of MDSCs in vivo. Besides, propranolol inhibited the expression of IL-6 in supernatant of 4T1 cells induced by isoproterenol and reduced the proportion of inducible MDSCs in vitro. Taken together, these data indicated that chronic stress may accumulate MDSCs via activation of β-adrenergic signaling and IL-6/STAT3 pathway, thereby promoting breast carcinoma metastasis.
format	article
author	Jiale an Lifeng Feng Jiling Ren Yafei Li Guangru Li Chang Liu Yong Yao Ye Yao Zecheng Jiang Yang Gao Yang Xu Yachen Wang Jing Li Jie Liu Lei Cao Zhi Qi Liang Yang
author_facet	Jiale an Lifeng Feng Jiling Ren Yafei Li Guangru Li Chang Liu Yong Yao Ye Yao Zecheng Jiang Yang Gao Yang Xu Yachen Wang Jing Li Jie Liu Lei Cao Zhi Qi Liang Yang
author_sort	Jiale an
title	Chronic stress promotes breast carcinoma metastasis by accumulating myeloid-derived suppressor cells through activating β-adrenergic signaling
title_short	Chronic stress promotes breast carcinoma metastasis by accumulating myeloid-derived suppressor cells through activating β-adrenergic signaling
title_full	Chronic stress promotes breast carcinoma metastasis by accumulating myeloid-derived suppressor cells through activating β-adrenergic signaling
title_fullStr	Chronic stress promotes breast carcinoma metastasis by accumulating myeloid-derived suppressor cells through activating β-adrenergic signaling
title_full_unstemmed	Chronic stress promotes breast carcinoma metastasis by accumulating myeloid-derived suppressor cells through activating β-adrenergic signaling
title_sort	chronic stress promotes breast carcinoma metastasis by accumulating myeloid-derived suppressor cells through activating β-adrenergic signaling
publisher	Taylor & Francis Group
publishDate	2021
url	https://doaj.org/article/17bd0be37f2145998c84f2ad46b4db48
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Chronic stress promotes breast carcinoma metastasis by accumulating myeloid-derived suppressor cells through activating β-adrenergic signaling

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