• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

循环髓系细胞浸润中枢神经系统介导胰腺癌恶病质。

Circulating myeloid cells invade the central nervous system to mediate cachexia during pancreatic cancer.

机构信息

Papé Family Pediatric Research Institute, Oregon Health & Science University, Portland, United States.

Medical Scientist Training Program, Oregon Health & Science University, Portland, United States.

出版信息

Elife. 2020 May 11;9:e54095. doi: 10.7554/eLife.54095.

DOI:10.7554/eLife.54095
PMID:32391790
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7253193/
Abstract

Weight loss and anorexia are common symptoms in cancer patients that occur prior to initiation of cancer therapy. Inflammation in the brain is a driver of these symptoms, yet cellular sources of neuroinflammation during malignancy are unknown. In a mouse model of pancreatic ductal adenocarcinoma (PDAC), we observed early and robust myeloid cell infiltration into the brain. Infiltrating immune cells were predominately neutrophils, which accumulated at a unique central nervous system entry portal called the velum interpositum, where they expressed CCR2. Pharmacologic CCR2 blockade and genetic deletion of both resulted in significantly decreased brain-infiltrating myeloid cells as well as attenuated cachexia during PDAC. Lastly, intracerebroventricular blockade of the purinergic receptor P2RX7 during PDAC abolished immune cell recruitment to the brain and attenuated anorexia. Our data demonstrate a novel function for the CCR2/CCL2 axis in recruiting neutrophils to the brain, which drives anorexia and muscle catabolism.

摘要

体重减轻和厌食是癌症患者在开始癌症治疗前常见的症状。大脑中的炎症是这些症状的驱动因素，但恶性肿瘤期间神经炎症的细胞来源尚不清楚。在胰腺导管腺癌 (PDAC) 的小鼠模型中，我们观察到早期和强烈的髓样细胞浸润到大脑中。浸润的免疫细胞主要是中性粒细胞，它们聚集在一个称为中间帆腔的独特的中枢神经系统进入门户，在那里它们表达 CCR2。药物 CCR2 阻断和 CCR2 和 CCL2 的基因缺失都导致大脑中浸润的髓样细胞明显减少，并在 PDAC 期间减轻恶病质。最后，在 PDAC 期间，中枢内脑室的嘌呤能受体 P2RX7 阻断消除了免疫细胞向大脑的募集，并减轻了厌食症。我们的数据表明 CCR2/CCL2 轴在将中性粒细胞募集到大脑中具有新的功能，这会导致厌食症和肌肉分解代谢。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac8d/7253193/3e0501d2c19a/elife-54095-resp-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac8d/7253193/6d2fc77b0ab2/elife-54095-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac8d/7253193/e5d1369475ea/elife-54095-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac8d/7253193/1def1bbbc8da/elife-54095-fig2-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac8d/7253193/53d2254eb738/elife-54095-fig2-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac8d/7253193/2f44640055aa/elife-54095-fig2-figsupp3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac8d/7253193/5d65a9adcc16/elife-54095-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac8d/7253193/365b1fe9a210/elife-54095-fig3-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac8d/7253193/97bdb869a3dc/elife-54095-fig3-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac8d/7253193/9840057a31e0/elife-54095-fig3-figsupp3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac8d/7253193/bb88e905f32d/elife-54095-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac8d/7253193/19795255d2e5/elife-54095-fig4-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac8d/7253193/a462a8319b66/elife-54095-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac8d/7253193/f0bb190a4ae7/elife-54095-fig5-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac8d/7253193/27aedade7bee/elife-54095-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac8d/7253193/67d0d074e2d1/elife-54095-fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac8d/7253193/e3898cf789a0/elife-54095-fig7-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac8d/7253193/1484b6f8f533/elife-54095-fig7-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac8d/7253193/d6fe7ca230cc/elife-54095-fig7-figsupp3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac8d/7253193/3dd0f8db3b1d/elife-54095-fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac8d/7253193/db40db7f787b/elife-54095-fig8-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac8d/7253193/56dae9c5ddc6/elife-54095-fig8-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac8d/7253193/3e0501d2c19a/elife-54095-resp-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac8d/7253193/6d2fc77b0ab2/elife-54095-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac8d/7253193/e5d1369475ea/elife-54095-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac8d/7253193/1def1bbbc8da/elife-54095-fig2-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac8d/7253193/53d2254eb738/elife-54095-fig2-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac8d/7253193/2f44640055aa/elife-54095-fig2-figsupp3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac8d/7253193/5d65a9adcc16/elife-54095-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac8d/7253193/365b1fe9a210/elife-54095-fig3-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac8d/7253193/97bdb869a3dc/elife-54095-fig3-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac8d/7253193/9840057a31e0/elife-54095-fig3-figsupp3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac8d/7253193/bb88e905f32d/elife-54095-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac8d/7253193/19795255d2e5/elife-54095-fig4-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac8d/7253193/a462a8319b66/elife-54095-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac8d/7253193/f0bb190a4ae7/elife-54095-fig5-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac8d/7253193/27aedade7bee/elife-54095-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac8d/7253193/67d0d074e2d1/elife-54095-fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac8d/7253193/e3898cf789a0/elife-54095-fig7-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac8d/7253193/1484b6f8f533/elife-54095-fig7-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac8d/7253193/d6fe7ca230cc/elife-54095-fig7-figsupp3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac8d/7253193/3dd0f8db3b1d/elife-54095-fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac8d/7253193/db40db7f787b/elife-54095-fig8-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac8d/7253193/56dae9c5ddc6/elife-54095-fig8-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac8d/7253193/3e0501d2c19a/elife-54095-resp-fig1.jpg

相似文献

1
Circulating myeloid cells invade the central nervous system to mediate cachexia during pancreatic cancer.循环髓系细胞浸润中枢神经系统介导胰腺癌恶病质。
Elife. 2020 May 11;9:e54095. doi: 10.7554/eLife.54095.
2
Targeting both tumour-associated CXCR2 neutrophils and CCR2 macrophages disrupts myeloid recruitment and improves chemotherapeutic responses in pancreatic ductal adenocarcinoma.靶向肿瘤相关 CXCR2 中性粒细胞和 CCR2 巨噬细胞可破坏髓系细胞募集并改善胰腺导管腺癌的化疗反应。
Gut. 2018 Jun;67(6):1112-1123. doi: 10.1136/gutjnl-2017-313738. Epub 2017 Dec 1.
3
CCR2 Expression in Neutrophils Plays a Critical Role in Their Migration Into the Joints in Rheumatoid Arthritis.CCR2 在中性粒细胞中的表达在类风湿关节炎中性粒细胞向关节迁移中起关键作用。
Arthritis Rheumatol. 2015 Jul;67(7):1751-9. doi: 10.1002/art.39117.
4
MyD88 signalling is critical in the development of pancreatic cancer cachexia.MyD88 信号通路在胰腺癌恶病质的发展中起着关键作用。
J Cachexia Sarcopenia Muscle. 2019 Apr;10(2):378-390. doi: 10.1002/jcsm.12377. Epub 2019 Jan 21.
5
Brain radiation injury leads to a dose- and time-dependent recruitment of peripheral myeloid cells that depends on CCR2 signaling.脑辐射损伤会导致外周髓样细胞的剂量和时间依赖性募集，这一过程依赖于CCR2信号传导。
J Neuroinflammation. 2016 Feb 3;13:30. doi: 10.1186/s12974-016-0496-8.
6
The systemic activin response to pancreatic cancer: implications for effective cancer cachexia therapy.胰腺癌的系统性激活素反应：对有效癌症恶病质治疗的启示。
J Cachexia Sarcopenia Muscle. 2019 Oct;10(5):1083-1101. doi: 10.1002/jcsm.12461. Epub 2019 Jul 8.
7
CCL2-CCR2 signaling promotes hepatic ischemia/reperfusion injury.CCL2-CCR2信号传导促进肝脏缺血/再灌注损伤。
J Surg Res. 2016 May 15;202(2):352-62. doi: 10.1016/j.jss.2016.02.029. Epub 2016 Mar 3.
8
The CCL2-CCR2 axis determines whether glomerular endocapillary hypercellularity or wire-loop lesions develop through glomerular macrophage and neutrophil infiltration in lupus nephritis.CCL2-CCR2 轴通过肾小球巨噬细胞和中性粒细胞浸润决定狼疮性肾炎中肾小球毛细血管内细胞增生还是线状环病变的发展。
J Pathol. 2024 Oct;264(2):174-185. doi: 10.1002/path.6331. Epub 2024 Jul 26.
9
Hepatic signal transducer and activator of transcription-3 signalling drives early-stage pancreatic cancer cachexia via suppressed ketogenesis.转录激活因子 3 信号驱动肝通过抑制酮体生成促进早期胰腺癌恶病质
J Cachexia Sarcopenia Muscle. 2024 Jun;15(3):975-988. doi: 10.1002/jcsm.13466. Epub 2024 Apr 17.
10
CC chemokine receptor 2 promotes recruitment of myeloid cells associated with insulin resistance in nonalcoholic fatty liver disease.CC 趋化因子受体 2 促进与非酒精性脂肪性肝病胰岛素抵抗相关的髓系细胞募集。
Am J Physiol Gastrointest Liver Physiol. 2018 Apr 1;314(4):G483-G493. doi: 10.1152/ajpgi.00213.2017. Epub 2018 Feb 8.

引用本文的文献

1
Cachexia Phenotyping Through Morphofunctional Assessment and Mitocondrial Biomarkers (GDF-15 and PGC-1α) in Idiopathic Pulmonary Fibrosis.通过形态功能评估和线粒体生物标志物（生长分化因子15和过氧化物酶体增殖物激活受体γ共激活因子1α）对特发性肺纤维化恶病质进行表型分析
Nutrients. 2025 Aug 24;17(17):2739. doi: 10.3390/nu17172739.
2
Bridging the tumor microenvironment: the pivotal role of cancer-associated fibroblasts in tumor cachexia development.连接肿瘤微环境：癌症相关成纤维细胞在肿瘤恶病质发展中的关键作用。
Mol Cancer. 2025 Jul 14;24(1):194. doi: 10.1186/s12943-025-02379-7.
3
Identification of the velum interpositum as a meningeal-CNS route for myeloid cell trafficking into the brain.

本文引用的文献

1
Microglia in the hypothalamus respond to tumor-derived factors and are protective against cachexia during pancreatic cancer.下丘脑的小胶质细胞对肿瘤来源的因子做出反应，并在胰腺癌期间对恶病质起保护作用。
Glia. 2020 Jul;68(7):1479-1494. doi: 10.1002/glia.23796. Epub 2020 Feb 10.
2
The TLR7/8 agonist R848 remodels tumor and host responses to promote survival in pancreatic cancer.TLR7/8 激动剂 R848 重塑肿瘤和宿主反应，促进胰腺癌的存活。
Nat Commun. 2019 Oct 15;10(1):4682. doi: 10.1038/s41467-019-12657-w.
3
Limitations of neutrophil depletion by anti-Ly6G antibodies in two heterogenic immunological models.
确认中间帆为骨髓细胞进入大脑的脑膜-中枢神经系统途径。
Neuron. 2025 Aug 6;113(15):2455-2473.e6. doi: 10.1016/j.neuron.2025.05.004. Epub 2025 Jun 3.
4
Hallmarks of Cancer Cachexia: Sexual Dimorphism in Related Pathways.癌症恶病质的特征：相关途径中的性别差异。
Int J Mol Sci. 2025 Apr 22;26(9):3952. doi: 10.3390/ijms26093952.
5
Cachexia Alters Central Nervous System Morphology and Functionality in Cancer Patients.恶病质改变癌症患者中枢神经系统的形态和功能。
J Cachexia Sarcopenia Muscle. 2025 Feb;16(1):e13742. doi: 10.1002/jcsm.13742.
6
Seeing through "brain fog": neuroimaging assessment and imaging biomarkers for cancer-related cognitive impairments.透过“脑雾”看问题：癌症相关认知障碍的神经影像学评估和影像学生物标志物。
Cancer Imaging. 2024 Nov 18;24(1):158. doi: 10.1186/s40644-024-00797-2.
7
Neuroscience in peripheral cancers: tumors hijacking nerves and neuroimmune crosstalk.外周癌症中的神经科学：肿瘤劫持神经与神经免疫相互作用
MedComm (2020). 2024 Oct 31;5(11):e784. doi: 10.1002/mco2.784. eCollection 2024 Nov.
8
Muscle inflammation is regulated by NF-κB from multiple cells to control distinct states of wasting in cancer cachexia.肌肉炎症受 NF-κB 从多种细胞调节，以控制癌症恶病质中不同的消耗状态。
Cell Rep. 2024 Nov 26;43(11):114925. doi: 10.1016/j.celrep.2024.114925. Epub 2024 Oct 30.
9
Immune System Disorder and Cancer-Associated Cachexia.免疫系统紊乱与癌症相关恶病质
Cancers (Basel). 2024 Apr 27;16(9):1709. doi: 10.3390/cancers16091709.
10
Peripheral-central network analysis of cancer cachexia status accompanied by the polarization of hypothalamic microglia with low expression of inhibitory immune checkpoint receptors.外周-中枢网络分析伴随抑制性免疫检查点受体低表达的下丘脑小胶质细胞极化的癌症恶病质状态。
Mol Brain. 2024 Apr 29;17(1):20. doi: 10.1186/s13041-024-01091-9.
抗 Ly6G 抗体对两种异源免疫模型中性粒细胞耗竭的局限性。
Immunol Lett. 2019 Aug;212:30-36. doi: 10.1016/j.imlet.2019.06.006. Epub 2019 Jun 18.
4
Pretreatment Cancer-Related Cognitive Impairment-Mechanisms and Outlook.癌症相关认知障碍的预处理——机制与展望
Cancers (Basel). 2019 May 16;11(5):687. doi: 10.3390/cancers11050687.
5
MyD88 signalling is critical in the development of pancreatic cancer cachexia.MyD88 信号通路在胰腺癌恶病质的发展中起着关键作用。
J Cachexia Sarcopenia Muscle. 2019 Apr;10(2):378-390. doi: 10.1002/jcsm.12377. Epub 2019 Jan 21.
6
Metabolic rewiring of macrophages by CpG potentiates clearance of cancer cells and overcomes tumor-expressed CD47-mediated 'don't-eat-me' signal.CpG 重塑巨噬细胞代谢可增强癌细胞清除作用，并克服肿瘤表达的 CD47 介导的“不要吃我”信号。
Nat Immunol. 2019 Jan 21;20(3):265-275. doi: 10.1038/s41590-018-0292-y.
7
Microglial cell loss after ischemic stroke favors brain neutrophil accumulation.缺血性脑卒中后小胶质细胞的丢失有利于脑中性粒细胞的聚集。
Acta Neuropathol. 2019 Feb;137(2):321-341. doi: 10.1007/s00401-018-1954-4. Epub 2018 Dec 22.
8
CNS lymphatic drainage and neuroinflammation are regulated by meningeal lymphatic vasculature.中枢神经系统的淋巴引流和神经炎症受脑膜淋巴血管调节。
Nat Neurosci. 2018 Oct;21(10):1380-1391. doi: 10.1038/s41593-018-0227-9. Epub 2018 Sep 17.
9
New role of P2X7 receptor in an Alzheimer's disease mouse model.P2X7 受体在阿尔茨海默病小鼠模型中的新作用。
Mol Psychiatry. 2019 Jan;24(1):108-125. doi: 10.1038/s41380-018-0108-3. Epub 2018 Jun 22.
10
TRIF is a key inflammatory mediator of acute sickness behavior and cancer cachexia.TRIF 是急性疾病行为和癌症恶病质的关键炎症介质。
Brain Behav Immun. 2018 Oct;73:364-374. doi: 10.1016/j.bbi.2018.05.021. Epub 2018 May 28.