Depression-Induced Neuropeptide Y Secretion Promotes Prostate Cancer Growth by Recruiting Myeloid Cells
Depression-Induced Neuropeptide Y Secretion Promotes Prostate Cancer Growth by Recruiting Myeloid Cells
复制标题
抑郁症诱导的神经肽 Y 分泌通过招募骨髓细胞促进前列腺癌生长
DOI：
10.1158/1078-0432.ccr-18-2912
复制
发表时间：
2019-04-15
影响因子：
11.5
通讯作者：
Yang, Yong
中科院分区：
文献类型：
--
作者：
Cheng, Yan;Tang, Xin-Ying;Yang, Yong
目的：心理抑郁症已被证明会使免疫系统失调并促进肿瘤进展。本研究的目的是调查心理抑郁如何改变前列腺癌的免疫特征。实验设计：我们在Myc-CaP荷瘤免疫活性FVB小鼠和自发性前列腺癌Hi-myc小鼠中使用了抑郁症小鼠模型。Transwell迁移和共培养试验用于评估Myc-CaP细胞引起的髓系细胞运输和细胞因子谱变化，Myc-CaP细胞已用去甲肾上腺素（NE）（抑郁症中主要升高的神经递质）处理。通过RNA-seq筛选与免疫细胞浸润相关的化学引诱剂。化学引诱物和免疫细胞浸润进一步证实了前列腺癌患者的临床样本与高得分的心理抑郁。结果如下：心理抑郁主要促进肿瘤相关巨噬细胞（TAM）肿瘤内浸润，这是由于脾脏和循环单核细胞骨髓源性抑制细胞动员。NE处理的Myc-CaP细胞释放的神经肽Y（neuropeptide Y，NPY）促进巨噬细胞的运输和IL 6的释放，从而激活前列腺癌细胞中的STAT 3信号通路。抑郁评分较高的前列腺癌患者的临床标本显示CD 68 + TAM浸润较高，NPY和IL 6表达较强。结论：抑郁症通过交感神经肽Y信号促进髓系细胞浸润和IL-6水平升高。交感神经肽Y抑制可能是一个有前途的策略，前列腺癌患者的心理抑郁评分高。见Mohammadpour等人的相关评论，第2363页
Purpose: Psychologic depression has been shown to dysregulate the immune system and promote tumor progression. The aim of this study is to investigate how psychologic depression alters the immune profiles in prostate cancer. Experimental Design: We used a murine model of depression in Myc-CaP tumor-bearing immunocompetent FVB mice and Hi-myc mice presenting with spontaneous prostate cancer. Transwell migration and coculture assays were used to evaluate myeloid cell trafficking and cytokine profile changes evoked by Myc-CaP cells that had been treated with norepinephrine (NE), a major elevated neurotransmitter in depression. Chemoattractant, which correlated with immune cell infiltration, was screened by RNA-seq. The chemoattractant and immune cell infiltration were further confirmed using clinical samples of patients with prostate cancer with a high score of psychologic depression. Results: Psychologic depression predominantly promoted tumor-associated macrophage (TAM) intratumor infiltrations, which resulted from spleen and circulating monocytic myeloid-derived suppressor cell mobilization. Neuropeptide Y (NPY) released from NE-treated Myc-CaP cells promotes macrophage trafficking and IL6 releasing, which activates STAT3 signaling pathway in prostate cancer cells. Clinical specimens from patients with prostate cancer with higher score of depression revealed higher CD68+ TAM infiltration and stronger NPY and IL6 expression. Conclusions: Depression promotes myeloid cell infiltration and increases IL6 levels by a sympathetic-NPY signal. Sympathetic-NPY inhibition may be a promising strategy for patients with prostate cancer with high score of psychologic depression. See related commentary by Mohammadpour et al., p. 2363