巨噬细胞与受体 VCAM-1 的结合在乳腺癌细胞向肺部浸润过程中传递存活信号。
Macrophage binding to receptor VCAM-1 transmits survival signals in breast cancer cells that invade the lungs.
机构信息
Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
出版信息
Cancer Cell. 2011 Oct 18;20(4):538-49. doi: 10.1016/j.ccr.2011.08.025.
Abstract
Aberrant expression of vascular cell adhesion molecule-1 (VCAM-1) in breast cancer cells is associated with lung relapse, but the role of VCAM-1 as a mediator of metastasis has remained unknown. We report that VCAM-1 provides a survival advantage to breast cancer cells that infiltrate leukocyte-rich microenvironments such as the lungs. VCAM-1 tethers metastasis-associated macrophages to cancer cells via counter-receptor α4-integrins. Clustering of cell surface VCAM-1, acting through Ezrin, triggers Akt activation and protects cancer cells from proapoptotic cytokines such as TRAIL. This prosurvival function of VCAM-1 can be blocked by antibodies against α4-integrins. Thus, newly disseminated cancer cells expressing VCAM-1 can thrive in leukocyte-rich microenvironments through juxtacrine activation of a VCAM-1-Ezrin-PI3K/Akt survival pathway.
摘要
血管细胞黏附分子-1（VCAM-1）在乳腺癌细胞中的异常表达与肺癌复发有关，但 VCAM-1 作为转移介质的作用尚不清楚。我们的研究表明，VCAM-1 为浸润富含白细胞的微环境（如肺部）的乳腺癌细胞提供了生存优势。VCAM-1 通过其对应受体α4 整合素将转移相关巨噬细胞与癌细胞连接在一起。细胞表面 VCAM-1 的聚集，通过埃兹蛋白（Ezrin）作用，触发 Akt 的激活，并保护癌细胞免受 TRAIL 等促凋亡细胞因子的影响。VCAM-1 的这种促进生存的功能可以被针对 α4 整合素的抗体阻断。因此，表达 VCAM-1 的新播散的癌细胞可以通过 VCAM-1-Ezrin-PI3K/Akt 生存途径的旁分泌激活在富含白细胞的微环境中茁壮成长。
相似文献
1
Macrophage binding to receptor VCAM-1 transmits survival signals in breast cancer cells that invade the lungs.巨噬细胞与受体 VCAM-1 的结合在乳腺癌细胞向肺部浸润过程中传递存活信号。
Cancer Cell. 2011 Oct 18;20(4):538-49. doi: 10.1016/j.ccr.2011.08.025.
2
Molecular pathways: VCAM-1 as a potential therapeutic target in metastasis.分子途径：VCAM-1 作为转移的潜在治疗靶点。
Clin Cancer Res. 2012 Oct 15;18(20):5520-5. doi: 10.1158/1078-0432.CCR-11-2904. Epub 2012 Aug 9.
3
High-density lipoprotein of patients with breast cancer complicated with type 2 diabetes mellitus promotes cancer cells adhesion to vascular endothelium via ICAM-1 and VCAM-1 upregulation.乳腺癌合并2型糖尿病患者的高密度脂蛋白通过上调细胞间黏附分子-1（ICAM-1）和血管细胞黏附分子-1（VCAM-1）促进癌细胞与血管内皮的黏附。
Breast Cancer Res Treat. 2016 Feb;155(3):441-55. doi: 10.1007/s10549-016-3696-0. Epub 2016 Feb 12.
4
Tumor-associated macrophages promote progression and the Warburg effect via CCL18/NF-kB/VCAM-1 pathway in pancreatic ductal adenocarcinoma.肿瘤相关巨噬细胞通过 CCL18/NF-kB/VCAM-1 通路促进胰腺导管腺癌的进展和瓦博格效应。
Cell Death Dis. 2018 May 1;9(5):453. doi: 10.1038/s41419-018-0486-0.
5
Vascular cell adhesion molecule-1 expression in human intestinal microvascular endothelial cells is regulated by PI 3-kinase/Akt/MAPK/NF-kappaB: inhibitory role of curcumin.人肠道微血管内皮细胞中血管细胞黏附分子-1的表达受PI 3-激酶/Akt/丝裂原活化蛋白激酶/核因子κB调控：姜黄素的抑制作用
Am J Physiol Gastrointest Liver Physiol. 2009 Aug;297(2):G259-68. doi: 10.1152/ajpgi.00087.2009. Epub 2009 Jun 11.
6
Kindlin-1 Promotes Pulmonary Breast Cancer Metastasis.Kindlin-1 促进肺转移乳腺癌的发生。
Cancer Res. 2018 Mar 15;78(6):1484-1496. doi: 10.1158/0008-5472.CAN-17-1518. Epub 2018 Jan 12.
7
8
Hydrophobic interaction mediating self-assembled nanoparticles of succinobucol suppress lung metastasis of breast cancer by inhibition of VCAM-1 expression.疏水性相互作用介导的丁烯二酸苏糖醇自组装纳米颗粒通过抑制 VCAM-1 表达抑制乳腺癌肺转移。
J Control Release. 2015 May 10;205:162-71. doi: 10.1016/j.jconrel.2015.01.015. Epub 2015 Jan 15.
9
Activation of VCAM-1 and its associated molecule CD44 leads to increased malignant potential of breast cancer cells.血管细胞黏附分子-1（VCAM-1）及其相关分子CD44的激活会导致乳腺癌细胞的恶性潜能增加。
Int J Mol Sci. 2014 Feb 27;15(3):3560-79. doi: 10.3390/ijms15033560.
10
VCAM-1 promotes osteolytic expansion of indolent bone micrometastasis of breast cancer by engaging α4β1-positive osteoclast progenitors.VCAM-1 通过与表达α4β1 的破骨细胞祖细胞结合，促进乳腺癌惰性骨微转移的溶骨性扩展。
Cancer Cell. 2011 Dec 13;20(6):701-14. doi: 10.1016/j.ccr.2011.11.002. Epub 2011 Dec 1.
引用本文的文献
1
predicts poor prognosis and modulates immune infiltration in gastric cancer: a TCGA-based bioinformatics study.预测胃癌预后不良并调节免疫浸润：一项基于TCGA的生物信息学研究
Front Genet. 2025 Aug 25;16:1602929. doi: 10.3389/fgene.2025.1602929. eCollection 2025.
2
Novel bioengineering strategies for drug delivery systems.药物递送系统的新型生物工程策略。
Appl Mater Today. 2023 Aug;33. doi: 10.1016/j.apmt.2023.101834. Epub 2023 Jun 9.
3
Metastasis-promoting functions of myeloid cells.髓系细胞的促转移功能。
Cancer Metastasis Rev. 2025 Jul 15;44(3):61. doi: 10.1007/s10555-025-10278-y.
4
Novel Computational Analysis Identifies Cytotoxic Lymphocyte-to-Monocyte Balance in Tumors as a Predictor of Recurrence-Free Survival in Colorectal Carcinoma.新型计算分析确定肿瘤中细胞毒性淋巴细胞与单核细胞的平衡是结直肠癌无复发生存的预测指标。
Ann Surg Oncol. 2025 Jun 21. doi: 10.1245/s10434-025-17599-w.
5
Macrophages in prostate cancer: dual roles in tumor progression and immune evasion.前列腺癌中的巨噬细胞：在肿瘤进展和免疫逃逸中的双重作用
J Transl Med. 2025 Jun 2;23(1):615. doi: 10.1186/s12967-025-06519-x.
6
Macrophages in the premetastatic and metastatic niche: key functions and therapeutic directions.前转移和转移微环境中的巨噬细胞：关键功能与治疗方向
J Transl Med. 2025 May 30;23(1):602. doi: 10.1186/s12967-025-06556-6.
7
Immune Evasion in Cancer Metastasis: An Unappreciated Role of Monocytes.癌症转移中的免疫逃逸：单核细胞的一个未被重视的作用。
Cancers (Basel). 2025 May 12;17(10):1638. doi: 10.3390/cancers17101638.
8
Unraveling the breast cancer tumor microenvironment: crucial factors influencing natural killer cell function and therapeutic strategies.解析乳腺癌肿瘤微环境：影响自然杀伤细胞功能的关键因素及治疗策略
Int J Biol Sci. 2025 Mar 24;21(6):2606-2628. doi: 10.7150/ijbs.108803. eCollection 2025.
9
Osteopontin in Chronic Inflammatory Diseases: Mechanisms, Biomarker Potential, and Therapeutic Strategies.慢性炎症性疾病中的骨桥蛋白：作用机制、生物标志物潜力及治疗策略
Biology (Basel). 2025 Apr 16;14(4):428. doi: 10.3390/biology14040428.
10
Premetastatic niche mechanics and organotropism in breast cancer.乳腺癌中的前转移生态位机制与器官趋向性
NPJ Biol Phys Mech. 2025;2(1):11. doi: 10.1038/s44341-025-00015-5. Epub 2025 Apr 3.
本文引用的文献
1
CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis.CCL2 招募炎症性单核细胞以促进乳腺癌转移。
Nature. 2011 Jun 8;475(7355):222-5. doi: 10.1038/nature10138.
2
mTOR: from growth signal integration to cancer, diabetes and ageing.mTOR：从生长信号整合到癌症、糖尿病和衰老。
Nat Rev Mol Cell Biol. 2011 Jan;12(1):21-35. doi: 10.1038/nrm3025. Epub 2010 Dec 15.
3
Phenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer.Claudin-low 型乳腺癌的表型和分子特征。
Breast Cancer Res. 2010;12(5):R68. doi: 10.1186/bcr2635. Epub 2010 Sep 2.
4
Macrophage diversity enhances tumor progression and metastasis.巨噬细胞多样性增强肿瘤的进展和转移。
Cell. 2010 Apr 2;141(1):39-51. doi: 10.1016/j.cell.2010.03.014.
5
Organizing the cell cortex: the role of ERM proteins.细胞皮层的组织：ERM 蛋白的作用。
Nat Rev Mol Cell Biol. 2010 Apr;11(4):276-87. doi: 10.1038/nrm2866.
6
IL-4 induces cathepsin protease activity in tumor-associated macrophages to promote cancer growth and invasion.IL-4 诱导肿瘤相关巨噬细胞中的组织蛋白酶蛋白酶活性，从而促进癌症生长和侵袭。
Genes Dev. 2010 Feb 1;24(3):241-55. doi: 10.1101/gad.1874010. Epub 2010 Jan 15.
7
Tumor self-seeding by circulating cancer cells.肿瘤细胞循环中的自我播种。
Cell. 2009 Dec 24;139(7):1315-26. doi: 10.1016/j.cell.2009.11.025.
8
Crohn's targeted therapy: myth or real goal?克罗恩病的靶向治疗：神话还是真正的目标？
Curr Drug Discov Technol. 2009 Dec;6(4):290-8. doi: 10.2174/157016309789869083.
9
Treatment of multiple sclerosis: role of natalizumab.多发性硬化症的治疗：那他珠单抗的作用。
Neurol Sci. 2009 Oct;30 Suppl 2:S155-8. doi: 10.1007/s10072-009-0147-2.
10
A distinct macrophage population mediates metastatic breast cancer cell extravasation, establishment and growth.一种独特的巨噬细胞群体介导了转移性乳腺癌细胞的渗出、定植和生长。
PLoS One. 2009 Aug 10;4(8):e6562. doi: 10.1371/journal.pone.0006562.
Zotero 插件