血管内皮生长因子/血管内皮生长因子受体与免疫细胞和癌细胞的关系：惊人还是前沿？
Relationship of VEGF/VEGFR with immune and cancer cells: staggering or forward?
作者信息
Li Yu-Ling, Zhao Hua, Ren Xiu-Bao
机构信息
Department of Biotherapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin 300060, China.
Department of Biotherapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin 300060, China; Key Laboratory of Cancer Immunology and Biotherapy, Research Center of Lung Cancer, Tianjin 300060, China.
出版信息
Cancer Biol Med. 2016 Jun;13(2):206-14. doi: 10.20892/j.issn.2095-3941.2015.0070.
Abstract
Vascular endothelial growth factor (VEGF) is primarily known as a proangiogenic factor and is one of the most important growth and survival factors affecting the vascular endothelium. However, recent studies have shown that VEGF also plays a vital role in the immune environment. In addition to the traditional growth factor role of VEGF and VEGF receptors (VEGFRs), they have a complicated relationship with various immune cells. VEGF also reportedly inhibits the differentiation and function of immune cells during hematopoiesis. Dendritic cells (DCs), macrophages, and lymphocytes further express certain types of VEGF receptors. VEGF can be secreted as well by tumor cells through the autocrine pathway and can stimulate the function of cancer stemness. This review will provide a paradigm shift in our understanding of the role of VEGF/VEGFR signaling in the immune and cancer environment.
摘要
血管内皮生长因子（VEGF）主要被认为是一种促血管生成因子，是影响血管内皮的最重要的生长和存活因子之一。然而，最近的研究表明，VEGF在免疫环境中也起着至关重要的作用。除了VEGF和VEGF受体（VEGFRs）的传统生长因子作用外，它们与各种免疫细胞有着复杂的关系。据报道，VEGF在造血过程中还会抑制免疫细胞的分化和功能。树突状细胞（DCs）、巨噬细胞和淋巴细胞进一步表达某些类型的VEGF受体。肿瘤细胞也可以通过自分泌途径分泌VEGF，并能刺激癌症干性的功能。本综述将为我们对VEGF/VEGFR信号在免疫和癌症环境中的作用的理解带来范式转变。
相似文献
1
Relationship of VEGF/VEGFR with immune and cancer cells: staggering or forward?血管内皮生长因子/血管内皮生长因子受体与免疫细胞和癌细胞的关系：惊人还是前沿？
Cancer Biol Med. 2016 Jun;13(2):206-14. doi: 10.20892/j.issn.2095-3941.2015.0070.
2
Inhibition of both paracrine and autocrine VEGF/ VEGFR-2 signaling pathways is essential to induce long-term remission of xenotransplanted human leukemias.抑制旁分泌和自分泌VEGF/VEGFR-2信号通路对于诱导异种移植的人类白血病长期缓解至关重要。
Proc Natl Acad Sci U S A. 2001 Sep 11;98(19):10857-62. doi: 10.1073/pnas.191117498.
3
Immunolocalization and expression of vascular endothelial growth factor receptors (VEGFRs) and neuropilins (NRPs) on keratinocytes in human epidermis.血管内皮生长因子受体（VEGFRs）和神经纤毛蛋白（NRPs）在人表皮角质形成细胞上的免疫定位及表达
Mol Med. 2006 Jul-Aug;12(7-8):127-36. doi: 10.2119/2006-00024.Man.
4
Vascular endothelial growth factor impairs the functional ability of dendritic cells through Id pathways.血管内皮生长因子通过Id通路损害树突状细胞的功能能力。
Biochem Biophys Res Commun. 2005 Aug 19;334(1):193-198. doi: 10.1016/j.bbrc.2005.06.065.
5
An autocrine loop directed by the vascular endothelial growth factor promotes invasiveness of human melanoma cells.由血管内皮生长因子引导的自分泌环促进人黑色素瘤细胞的侵袭性。
Int J Oncol. 2005 Dec;27(6):1625-32.
6
Expression of vascular endothelial growth factor receptors on tumor cells in head and neck squamous cell carcinoma.头颈部鳞状细胞癌中肿瘤细胞上血管内皮生长因子受体的表达
Arch Otolaryngol Head Neck Surg. 2003 Aug;129(8):882-8. doi: 10.1001/archotol.129.8.882.
7
Role of hypoxia in inhibiting dendritic cells by VEGF signaling in tumor microenvironments: mechanism and application.缺氧在肿瘤微环境中通过VEGF信号传导抑制树突状细胞的作用：机制与应用
Am J Cancer Res. 2021 Aug 15;11(8):3777-3793. eCollection 2021.
8
Gene expression profile of vascular endothelial growth factor (VEGF) and its receptors in various cell types of the canine lymph node using laser capture microdissection (LCM).利用激光捕获显微切割技术（LCM）分析犬淋巴结不同细胞类型中血管内皮生长因子（VEGF）及其受体的基因表达谱。
Vet Immunol Immunopathol. 2011 Apr 15;140(3-4):207-14. doi: 10.1016/j.vetimm.2010.12.005. Epub 2010 Dec 15.
9
Autocrine vascular endothelial growth factor signalling in breast cancer. Evidence from cell lines and primary breast cancer cultures in vitro.乳腺癌中的自分泌血管内皮生长因子信号传导。来自体外细胞系和原发性乳腺癌培养物的证据。
Angiogenesis. 2005;8(3):197-204. doi: 10.1007/s10456-005-9010-0. Epub 2005 Nov 19.
10
Hypoxia-induced epithelial VEGF-C/VEGFR-3 upregulation in carcinoma cell lines.缺氧诱导癌细胞系中上皮细胞VEGF-C/VEGFR-3上调。
Int J Oncol. 2008 Mar;32(3):585-92.
引用本文的文献
1
Cytokine Networks in Triple-Negative Breast Cancer: Mechanisms, Therapeutic Targets, and Emerging Strategies.三阴性乳腺癌中的细胞因子网络：机制、治疗靶点及新兴策略
Biomedicines. 2025 Aug 8;13(8):1945. doi: 10.3390/biomedicines13081945.
2
Long-term DNA methylation changes mediate heterologous cytokine responses after BCG vaccination.长期的DNA甲基化变化介导卡介苗接种后的异源细胞因子反应。
Genome Biol. 2025 Jul 9;26(1):180. doi: 10.1186/s13059-025-03611-9.
3
The expression and relationship of VEGF and MVD in type I endometrial cancer.VEGF与微血管密度（MVD）在I型子宫内膜癌中的表达及关系
Medicine (Baltimore). 2025 Jun 27;104(26):e42945. doi: 10.1097/MD.0000000000042945.
4
AI-Driven Multiscale Study on the Mechanism of Polygonati Rhizoma in Regulating Immune Function in STAD.基于人工智能的多尺度研究：黄精调控胃癌免疫功能的机制
ACS Omega. 2025 May 11;10(19):19770-19796. doi: 10.1021/acsomega.5c00981. eCollection 2025 May 20.
5
Development and Validation of an Extracellular Matrix Gene Expression Signature for Prognostic Prediction in Patients with Uveal Melanoma.葡萄膜黑色素瘤患者预后预测的细胞外基质基因表达特征的开发与验证
Int J Mol Sci. 2025 May 1;26(9):4317. doi: 10.3390/ijms26094317.
6
Natural Products as Novel Therapeutic Agents for Triple-Negative Breast Cancer: Current Evidence, Mechanisms, Challenges, and Opportunities.天然产物作为三阴性乳腺癌的新型治疗药物：当前证据、作用机制、挑战与机遇
Molecules. 2025 Mar 7;30(6):1201. doi: 10.3390/molecules30061201.
7
Vascular endothelial growth factor A: friend or foe in the pathogenesis of HIV and SARS-CoV-2 infections?血管内皮生长因子A：在HIV和SARS-CoV-2感染发病机制中是友还是敌？
Front Cell Infect Microbiol. 2025 Feb 11;14:1458195. doi: 10.3389/fcimb.2024.1458195. eCollection 2024.
8
EZH2 elicits CD8 T-cell desert in esophageal squamous cell carcinoma via suppressing CXCL9 and dendritic cells.EZH2通过抑制CXCL9和树突状细胞在食管鳞状细胞癌中引发CD8 T细胞耗竭。
Commun Biol. 2024 Dec 19;7(1):1645. doi: 10.1038/s42003-024-07341-9.
9
Dual role of vascular endothelial growth factor-C in post-stroke recovery.血管内皮生长因子-C在中风后恢复中的双重作用。
J Exp Med. 2025 Feb 3;222(2). doi: 10.1084/jem.20231816. Epub 2024 Dec 12.
10
MACC1 revisited - an in-depth review of a master of metastasis.重新审视MACC1——对转移“大师”的深入回顾
Biomark Res. 2024 Nov 23;12(1):146. doi: 10.1186/s40364-024-00689-4.
本文引用的文献
1
Activation of vascular endothelial growth factor receptor-3 in macrophages restrains TLR4-NF-κB signaling and protects against endotoxin shock.血管内皮生长因子受体-3 在巨噬细胞中的激活抑制 TLR4-NF-κB 信号通路并防止内毒素休克。
Immunity. 2014 Apr 17;40(4):501-14. doi: 10.1016/j.immuni.2014.01.013. Epub 2014 Mar 20.
2
HIF expression and the role of hypoxic microenvironments within primary tumours as protective sites driving cancer stem cell renewal and metastatic progression.缺氧诱导因子表达和原发性肿瘤缺氧微环境的作用作为保护性部位，驱动癌症干细胞更新和转移进展。
Carcinogenesis. 2013 Aug;34(8):1699-707. doi: 10.1093/carcin/bgt209. Epub 2013 Jun 5.
3
Macrophage biology in development, homeostasis and disease.发育、稳态和疾病中的巨噬细胞生物学。
Nature. 2013 Apr 25;496(7446):445-55. doi: 10.1038/nature12034.
4
Soluble vascular endothelial growth factor receptor 3 is essential for corneal alymphaticity.可溶性血管内皮生长因子受体 3 对于角膜无淋巴管状态至关重要。
Blood. 2013 May 16;121(20):4242-9. doi: 10.1182/blood-2012-08-453043. Epub 2013 Mar 8.
5
Insulin-like growth factor receptor I (IGF-IR) and vascular endothelial growth factor receptor 2 (VEGFR-2) are expressed on the circulating epithelial tumor cells of breast cancer patients.胰岛素样生长因子受体 I（IGF-IR）和血管内皮生长因子受体 2（VEGFR-2）在乳腺癌患者的循环上皮肿瘤细胞上表达。
PLoS One. 2013;8(2):e56836. doi: 10.1371/journal.pone.0056836. Epub 2013 Feb 13.
6
VEGF directly suppresses activation of T cells from ascites secondary to ovarian cancer via VEGF receptor type 2.VEGF 通过血管内皮生长因子受体 2 直接抑制卵巢癌腹水继发 T 细胞的活化。
Br J Cancer. 2012 Nov 20;107(11):1869-75. doi: 10.1038/bjc.2012.468.
7
Neuropilin 1 deficiency on CD4+Foxp3+ regulatory T cells impairs mouse melanoma growth.CD4+Foxp3+ 调节性 T 细胞中神经纤毛蛋白 1 缺乏可抑制小鼠黑色素瘤生长。
J Exp Med. 2012 Oct 22;209(11):2001-16. doi: 10.1084/jem.20111497. Epub 2012 Oct 8.
8
Critical role of VEGF-C/VEGFR-3 signaling in innate and adaptive immune responses in experimental obliterative bronchiolitis.VEGF-C/VEGFR-3 信号在实验性闭塞性细支气管炎中固有和适应性免疫反应中的关键作用。
Am J Pathol. 2012 Nov;181(5):1607-20. doi: 10.1016/j.ajpath.2012.07.021. Epub 2012 Sep 7.
9
Signal transduction by vascular endothelial growth factor receptors.血管内皮生长因子受体的信号转导。
Cold Spring Harb Perspect Med. 2012 Jul;2(7):a006502. doi: 10.1101/cshperspect.a006502.
10
Neuropilin-1 stimulates tumor growth by increasing fibronectin fibril assembly in the tumor microenvironment.神经纤毛蛋白 1 通过增加肿瘤微环境中的纤维连接蛋白原纤维组装来刺激肿瘤生长。
Cancer Res. 2012 Aug 15;72(16):4047-59. doi: 10.1158/0008-5472.CAN-11-3907. Epub 2012 Jun 27.
Zotero 插件