• 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

肿瘤分泌的 GRP78 促进肝微环境中前转移龛的建立。

Tumor-Secreted GRP78 Promotes the Establishment of a Pre-metastatic Niche in the Liver Microenvironment.

机构信息

Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan, China.

出版信息

Front Immunol. 2020 Sep 29;11:584458. doi: 10.3389/fimmu.2020.584458. eCollection 2020.

DOI:10.3389/fimmu.2020.584458
PMID:33133103
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7550426/
Abstract

The liver is an immunologically tolerant organ and a common site of distant metastasis for various cancers. The expression levels of glucose-regulated protein 78 (GRP78) have been associated with tumor malignancy. Secretory GRP78 (sGRP78) released from tumor cells contributes to the establishment of an immunosuppressive tumor microenvironment by regulating cytokine production in macrophages and dendritic cells (DCs). However, the role of sGRP78 on tumor cell colonization and metastasis in the liver remains unclear. Herein, we found that GRP78 was expressed at higher levels in the liver compared to other tissues and organs. We performed intravital imaging using a sGRP78-overexpressing breast cancer cell line (E0771) and found that sGRP78 interacted with dendritic cells (DCs) and F4/80 macrophages in the liver. Importantly, sGRP78 overexpression inhibited DC activation and induced M2-like polarization in F4/80 macrophages. Moreover, sGRP78 overexpression enhanced TGF-β production in the liver. In conclusion, sGRP78 promotes tumor cell colonization in the liver by remodeling the tumor microenvironment and promoting immune tolerance. The ability of sGRP78-targeting strategies to prevent or treat liver metastasis should be further examined.

摘要

肝脏是一个免疫耐受器官，也是各种癌症远处转移的常见部位。葡萄糖调节蛋白 78（GRP78）的表达水平与肿瘤恶性程度有关。肿瘤细胞释放的分泌型 GRP78（sGRP78）通过调节巨噬细胞和树突状细胞（DC）中的细胞因子产生，有助于建立免疫抑制性肿瘤微环境。然而，sGRP78 对肿瘤细胞在肝脏中的定植和转移的作用尚不清楚。在此，我们发现与其他组织和器官相比，GRP78 在肝脏中的表达水平更高。我们使用过表达 sGRP78 的乳腺癌细胞系（E0771）进行活体成像，发现 sGRP78 与肝脏中的树突状细胞（DC）和 F4/80 巨噬细胞相互作用。重要的是，sGRP78 的过表达抑制了 DC 的激活，并诱导了 F4/80 巨噬细胞向 M2 样极化。此外，sGRP78 的过表达增强了肝脏中 TGF-β的产生。总之，sGRP78 通过重塑肿瘤微环境和促进免疫耐受来促进肿瘤细胞在肝脏中的定植。应该进一步研究 sGRP78 靶向策略预防或治疗肝转移的能力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f5f/7550426/0ed5ac75b2bc/fimmu-11-584458-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f5f/7550426/4de98388708f/fimmu-11-584458-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f5f/7550426/172497a9c9d0/fimmu-11-584458-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f5f/7550426/78f304abd5a8/fimmu-11-584458-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f5f/7550426/60a4fd35f8bb/fimmu-11-584458-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f5f/7550426/5065b80b3ee2/fimmu-11-584458-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f5f/7550426/0ed5ac75b2bc/fimmu-11-584458-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f5f/7550426/4de98388708f/fimmu-11-584458-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f5f/7550426/172497a9c9d0/fimmu-11-584458-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f5f/7550426/78f304abd5a8/fimmu-11-584458-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f5f/7550426/60a4fd35f8bb/fimmu-11-584458-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f5f/7550426/5065b80b3ee2/fimmu-11-584458-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f5f/7550426/0ed5ac75b2bc/fimmu-11-584458-g006.jpg

相似文献

1
Tumor-Secreted GRP78 Promotes the Establishment of a Pre-metastatic Niche in the Liver Microenvironment.肿瘤分泌的 GRP78 促进肝微环境中前转移龛的建立。
Front Immunol. 2020 Sep 29;11:584458. doi: 10.3389/fimmu.2020.584458. eCollection 2020.
2
Cell Surface GRP78 Accelerated Breast Cancer Cell Proliferation and Migration by Activating STAT3.细胞表面GRP78通过激活STAT3促进乳腺癌细胞增殖和迁移。
PLoS One. 2015 May 14;10(5):e0125634. doi: 10.1371/journal.pone.0125634. eCollection 2015.
3
Cell surface GRP78 promotes stemness in normal and neoplastic cells.细胞表面 GRP78 促进正常和肿瘤细胞的干性。
Sci Rep. 2020 Feb 26;10(1):3474. doi: 10.1038/s41598-020-60269-y.
4
Cancer cells resistant to therapy promote cell surface relocalization of GRP78 which complexes with PI3K and enhances PI(3,4,5)P3 production.对治疗有抗性的癌细胞会促进 GRP78 的细胞表面重定位，GRP78 与 PI3K 形成复合物，从而增强 PI(3,4,5)P3 的产生。
PLoS One. 2013 Nov 11;8(11):e80071. doi: 10.1371/journal.pone.0080071. eCollection 2013.
5
CYP4A in tumor-associated macrophages promotes pre-metastatic niche formation and metastasis.肿瘤相关巨噬细胞中的CYP4A促进前转移微环境的形成和转移。
Oncogene. 2017 Aug 31;36(35):5045-5057. doi: 10.1038/onc.2017.118. Epub 2017 May 8.
6
Splenectomy reduces lung metastases and tumoral and metastatic niche inflammation.脾切除术可减少肺转移和肿瘤及转移灶微环境炎症。
Int J Cancer. 2019 Nov 1;145(9):2509-2520. doi: 10.1002/ijc.32378. Epub 2019 May 13.
7
Tumor-secreted GRP78 facilitates the migration of macrophages into tumors by promoting cytoskeleton remodeling.肿瘤分泌的 GRP78 通过促进细胞骨架重塑促进巨噬细胞向肿瘤迁移。
Cell Signal. 2019 Aug;60:1-16. doi: 10.1016/j.cellsig.2019.04.004. Epub 2019 Apr 5.
8
Induction of tolerogenic dendritic cells by activated TGF-β/Akt/Smad2 signaling in RIG-I-deficient stemness-high human liver cancer cells.RIG-I 缺陷型干性高的人肝癌细胞中激活的 TGF-β/Akt/Smad2 信号诱导免疫耐受树突状细胞。
BMC Cancer. 2019 May 14;19(1):439. doi: 10.1186/s12885-019-5670-9.
9
M2 polarization of macrophages by Oncostatin M in hypoxic tumor microenvironment is mediated by mTORC2 and promotes tumor growth and metastasis.缺氧肿瘤微环境中抑瘤素 M 诱导的巨噬细胞 M2 极化是由 mTORC2 介导的，并促进肿瘤生长和转移。
Cytokine. 2019 Jun;118:130-143. doi: 10.1016/j.cyto.2018.03.032. Epub 2018 Apr 3.
10
Targeting the Stat6 pathway in tumor-associated macrophages reduces tumor growth and metastatic niche formation in breast cancer.靶向肿瘤相关巨噬细胞中的 Stat6 通路可减少乳腺癌中的肿瘤生长和转移龛形成。
FASEB J. 2018 Feb;32(2):969-978. doi: 10.1096/fj.201700629R. Epub 2018 Jan 3.

引用本文的文献

1
Bridging the Gap in Breast Cancer Dormancy: Models, Mechanisms, and Translational Challenges.弥合乳腺癌休眠的差距：模型、机制及转化挑战
Pharmaceuticals (Basel). 2025 Jun 26;18(7):961. doi: 10.3390/ph18070961.
2
Endoplasmic Reticulum Stress in Cancer.癌症中的内质网应激
MedComm (2020). 2025 Jun 19;6(7):e70263. doi: 10.1002/mco2.70263. eCollection 2025 Jul.
3
Heterogeneous tissue-specific macrophages orchestrate metastatic organotropism of breast cancer: implications for promising therapeutics.异质性组织特异性巨噬细胞调控乳腺癌的转移器官趋向性：对有前景疗法的启示

本文引用的文献

1
Endoplasmic Reticulum Stress Pathway, the Unfolded Protein Response, Modulates Immune Function in the Tumor Microenvironment to Impact Tumor Progression and Therapeutic Response.内质网应激途径、未折叠蛋白反应调节肿瘤微环境中的免疫功能，影响肿瘤进展和治疗反应。
Int J Mol Sci. 2019 Dec 25;21(1):169. doi: 10.3390/ijms21010169.
2
Impairment of NKG2D-Mediated Tumor Immunity by TGF-β.转化生长因子-β（TGF-β）对 NKG2D 介导的肿瘤免疫的抑制作用。
Front Immunol. 2019 Nov 15;10:2689. doi: 10.3389/fimmu.2019.02689. eCollection 2019.
3
Cell Surface GRP78 as a Death Receptor and an Anticancer Drug Target.
J Transl Med. 2025 Jun 20;23(1):692. doi: 10.1186/s12967-025-06660-7.
4
Intravital Imaging of Immune Responses in the Cancer Microenvironment.癌症微环境中免疫反应的活体成像
Cancer Med. 2025 Apr;14(8):e70899. doi: 10.1002/cam4.70899.
5
MiR-769-5p of macrophage exosomes induced by GRP78 promotes stemness and chemoresistance in colorectal cancer.GRP78诱导的巨噬细胞外泌体中的MiR-769-5p促进结直肠癌的干性和化疗耐药性。
Cell Death Dis. 2025 Mar 5;16(1):156. doi: 10.1038/s41419-025-07466-7.
6
Liver Metastasis in Cancer: Molecular Mechanisms and Management.癌症中的肝转移：分子机制与治疗
MedComm (2020). 2025 Feb 27;6(3):e70119. doi: 10.1002/mco2.70119. eCollection 2025 Mar.
7
GRP78 in Glioma Progression and Therapy: Implications for Targeted Approaches.胶质瘤进展与治疗中的GRP78：对靶向治疗方法的启示
Biomedicines. 2025 Feb 6;13(2):382. doi: 10.3390/biomedicines13020382.
8
Immune dynamics shaping pre-metastatic and metastatic niches in liver metastases: from molecular mechanisms to therapeutic strategies.免疫动力学塑造肝转移中的前转移和转移生态位：从分子机制到治疗策略。
Mol Cancer. 2024 Nov 14;23(1):254. doi: 10.1186/s12943-024-02171-z.
9
LncRNAs in tumor metabolic reprogramming and tumor microenvironment remodeling.长链非编码 RNA 在肿瘤代谢重编程和肿瘤微环境重塑中的作用。
Front Immunol. 2024 Oct 30;15:1467151. doi: 10.3389/fimmu.2024.1467151. eCollection 2024.
10
Pre-metastatic niche: formation, characteristics and therapeutic implication.转移前生态位：形成、特征及治疗意义
Signal Transduct Target Ther. 2024 Sep 25;9(1):236. doi: 10.1038/s41392-024-01937-7.
细胞表面GRP78作为一种死亡受体和抗癌药物靶点。
Cancers (Basel). 2019 Nov 13;11(11):1787. doi: 10.3390/cancers11111787.
4
CXCR1 Mediates the Development of Monocyte-Derived Dendritic Cells during Hepatic Inflammation.CXCR1 介导肝炎症期间单核细胞衍生树突状细胞的发育。
Cells. 2019 Sep 18;8(9):1099. doi: 10.3390/cells8091099.
5
GRP78-targeted ferritin nanocaged ultra-high dose of doxorubicin for hepatocellular carcinoma therapy.GRP78 靶向铁蛋白纳米笼超高剂量阿霉素治疗肝细胞癌。
Theranostics. 2019 Apr 12;9(8):2167-2182. doi: 10.7150/thno.30867. eCollection 2019.
6
Tumor-secreted GRP78 facilitates the migration of macrophages into tumors by promoting cytoskeleton remodeling.肿瘤分泌的 GRP78 通过促进细胞骨架重塑促进巨噬细胞向肿瘤迁移。
Cell Signal. 2019 Aug;60:1-16. doi: 10.1016/j.cellsig.2019.04.004. Epub 2019 Apr 5.
7
Hepatocytes direct the formation of a pro-metastatic niche in the liver.肝细胞在肝脏中诱导形成有利于转移的生态位。
Nature. 2019 Mar;567(7747):249-252. doi: 10.1038/s41586-019-1004-y. Epub 2019 Mar 6.
8
Anti-NKG2A mAb Is a Checkpoint Inhibitor that Promotes Anti-tumor Immunity by Unleashing Both T and NK Cells.抗 NKG2A mAb 是一种检查点抑制剂，通过释放 T 细胞和 NK 细胞来促进抗肿瘤免疫。
Cell. 2018 Dec 13;175(7):1731-1743.e13. doi: 10.1016/j.cell.2018.10.014. Epub 2018 Nov 29.
9
Natural Killer Cells in Liver Disease and Hepatocellular Carcinoma and the NK Cell-Based Immunotherapy.自然杀伤细胞在肝脏疾病和肝细胞癌中的作用及基于 NK 细胞的免疫治疗。
J Immunol Res. 2018 Sep 4;2018:1206737. doi: 10.1155/2018/1206737. eCollection 2018.
10
Proapoptotic Cyclic Peptide BC71 Targets Cell-Surface GRP78 and Functions as an Anticancer Therapeutic in Mice.促凋亡环肽 BC71 靶向细胞表面 GRP78 并在小鼠中作为抗癌治疗剂发挥作用。
EBioMedicine. 2018 Jul;33:22-32. doi: 10.1016/j.ebiom.2018.06.004. Epub 2018 Jun 12.