• 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

瘦素在乳腺癌中的促血管生成特征与 IL-1 信号有关。

Leptin pro-angiogenic signature in breast cancer is linked to IL-1 signalling.

机构信息

Department of Microbiology, Morehouse School of Medicine, Atlanta, GA 30310, USA.

出版信息

Br J Cancer. 2011 Jan 4;104(1):128-37. doi: 10.1038/sj.bjc.6606013. Epub 2010 Dec 7.

DOI:10.1038/sj.bjc.6606013
PMID:21139583
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3039812/
Abstract

BACKGROUND

Leptin and interleukin-1 (IL-1) upregulate vascular endothelial growth factor (VEGF), promote angiogenesis and are related to worse prognosis of breast cancer. However, it is unknown whether leptin regulates IL-1, and whether these effects are related to leptin-induction of VEGF/VEGFR2 in breast cancer.

METHODS

Several genetic and pharmacological approaches were used to determine the mechanisms involved in leptin regulation of IL-1 system (IL-1α, IL-1β, IL-1Ra and IL-1R tI) and the impact of IL-1 signalling on leptin-induced VEGF/VEGFR2 expression in mouse mammary cancer 4T1 cells (a model that resembles invasive and highly metastatic human breast cancer).

RESULTS

Leptin increased protein and mRNA levels of all components of the IL-1 system. IL-1 upregulation involved leptin activation of JAK2/STAT3, MAPK/ERK 1/2, PI-3K/AKT1, PKC, p38 and JNK. Leptin-induced phosphorylation of mTOR/4E-BP1 increased IL-1β and IL-1Ra expression, but downregulated IL-1α. Leptin upregulation of IL-1α promoter was linked to SP1 and NF-κB transcription factors. In addition, leptin receptor (Ob-Rb) was upregulated by leptin. Interestingly, leptin upregulation of VEGF/VEGFR2 was partially mediated by IL-1/IL-1R tI signalling.

CONCLUSIONS

We show for the first time that leptin induces several signalling pathways to upregulate the translational and transcriptional expression of IL-1 system in breast cancer cells. Moreover, leptin upregulation of VEGF/VEGFR2 was impaired by IL-1 signalling blockade. These data suggest that leptin pro-angiogenic signature in breast cancer is linked to, or regulated, in part by IL-1 signalling.

摘要

背景

瘦素和白细胞介素-1（IL-1）上调血管内皮生长因子（VEGF），促进血管生成，并与乳腺癌的预后不良相关。然而，目前尚不清楚瘦素是否调节 IL-1，以及这些作用是否与瘦素诱导的乳腺癌中 VEGF/VEGFR2 有关。

方法

采用多种遗传和药理学方法，确定瘦素调节 IL-1 系统（IL-1α、IL-1β、IL-1Ra 和 IL-1R tI）的机制，以及 IL-1 信号对瘦素诱导的 4T1 细胞（一种类似于侵袭性和高度转移性人类乳腺癌的模型）中 VEGF/VEGFR2 表达的影响。

结果

瘦素增加了 IL-1 系统的所有成分的蛋白和 mRNA 水平。IL-1 的上调涉及瘦素激活 JAK2/STAT3、MAPK/ERK 1/2、PI-3K/AKT1、PKC、p38 和 JNK。瘦素诱导的 mTOR/4E-BP1 磷酸化增加了 IL-1β 和 IL-1Ra 的表达，但下调了 IL-1α。瘦素对 IL-1α 启动子的上调与 SP1 和 NF-κB 转录因子有关。此外，瘦素还上调了瘦素受体（Ob-Rb）。有趣的是，瘦素对 VEGF/VEGFR2 的上调部分是由 IL-1/IL-1R tI 信号介导的。

结论

我们首次表明，瘦素通过多种信号通路诱导乳腺癌细胞中 IL-1 系统的翻译和转录表达上调。此外，IL-1 信号阻断削弱了瘦素对 VEGF/VEGFR2 的上调。这些数据表明，瘦素在乳腺癌中的促血管生成特征与 IL-1 信号有关，或部分受其调节。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddb5/3039812/5e980b64449b/6606013f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddb5/3039812/e362e81ffd33/6606013f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddb5/3039812/6b062b047936/6606013f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddb5/3039812/6506700ecf9f/6606013f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddb5/3039812/13f8cd937f86/6606013f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddb5/3039812/cb0d219dd8c5/6606013f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddb5/3039812/0a46eb02cd89/6606013f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddb5/3039812/df85cd7c2185/6606013f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddb5/3039812/5e980b64449b/6606013f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddb5/3039812/e362e81ffd33/6606013f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddb5/3039812/6b062b047936/6606013f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddb5/3039812/6506700ecf9f/6606013f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddb5/3039812/13f8cd937f86/6606013f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddb5/3039812/cb0d219dd8c5/6606013f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddb5/3039812/0a46eb02cd89/6606013f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddb5/3039812/df85cd7c2185/6606013f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddb5/3039812/5e980b64449b/6606013f8.jpg

相似文献

1
Leptin pro-angiogenic signature in breast cancer is linked to IL-1 signalling.瘦素在乳腺癌中的促血管生成特征与 IL-1 信号有关。
Br J Cancer. 2011 Jan 4;104(1):128-37. doi: 10.1038/sj.bjc.6606013. Epub 2010 Dec 7.
2
Notch, IL-1 and leptin crosstalk outcome (NILCO) is critical for leptin-induced proliferation, migration and VEGF/VEGFR-2 expression in breast cancer.Notch、IL-1 和瘦素相互作用的结果（NILCO）对于瘦素诱导的乳腺癌增殖、迁移和 VEGF/VEGFR-2 表达至关重要。
PLoS One. 2011;6(6):e21467. doi: 10.1371/journal.pone.0021467. Epub 2011 Jun 23.
3
Leptin upregulates VEGF in breast cancer via canonic and non-canonical signalling pathways and NFkappaB/HIF-1alpha activation.瘦素通过经典和非经典信号通路以及 NFkappaB/HIF-1alpha 激活上调乳腺癌中的 VEGF。
Cell Signal. 2010 Sep;22(9):1350-62. doi: 10.1016/j.cellsig.2010.05.003. Epub 2010 May 11.
4
Leptin regulation of proangiogenic molecules in benign and cancerous endometrial cells.瘦素对良性和癌性子宫内膜细胞中促血管生成分子的调节作用。
Int J Cancer. 2008 Dec 15;123(12):2782-90. doi: 10.1002/ijc.23887.
5
A hypoxia-dependent upregulation of hypoxia-inducible factor-1 by nuclear factor-κB promotes gastric tumour growth and angiogenesis.核因子-κB 依赖性缺氧诱导因子-1 的上调促进胃肿瘤生长和血管生成。
Br J Cancer. 2011 Jan 4;104(1):166-74. doi: 10.1038/sj.bjc.6606020. Epub 2010 Nov 30.
6
Insulin-dependent leptin expression in breast cancer cells.乳腺癌细胞中胰岛素依赖性瘦素表达
Cancer Res. 2008 Jun 15;68(12):4919-27. doi: 10.1158/0008-5472.CAN-08-0642.
7
Leptin-signaling inhibition results in efficient anti-tumor activity in estrogen receptor positive or negative breast cancer.瘦素信号抑制导致雌激素受体阳性或阴性乳腺癌的有效抗肿瘤活性。
Breast Cancer Res. 2009;11(3):R36. doi: 10.1186/bcr2321. Epub 2009 Jun 16.
8
The nuclear factor-κB correlates with increased expression of interleukin-6 and promotes progression of gastric carcinoma.核因子-κB 与白细胞介素-6 的表达增加相关，并促进胃癌的进展。
Oncol Rep. 2013 Jan;29(1):34-8. doi: 10.3892/or.2012.2089. Epub 2012 Oct 19.
9
Activation of IL-8 via PI3K/Akt-dependent pathway is involved in leptin-mediated epithelial-mesenchymal transition in human breast cancer cells.通过PI3K/Akt依赖性途径激活IL-8参与了人乳腺癌细胞中瘦素介导的上皮-间质转化。
Cancer Biol Ther. 2015;16(8):1220-30. doi: 10.1080/15384047.2015.1056409. Epub 2015 Jun 29.
10
(-)-Epigallocatechin-3-gallate inhibits VEGF expression induced by IL-6 via Stat3 in gastric cancer.(-)-表没食子儿茶素没食子酸酯通过 Stat3 抑制 IL-6 诱导的胃癌中 VEGF 的表达。
World J Gastroenterol. 2011 May 14;17(18):2315-25. doi: 10.3748/wjg.v17.i18.2315.

引用本文的文献

1
Obesity-cancer axis crosstalk: Molecular insights and therapeutic approaches.肥胖-癌症轴的相互作用：分子见解与治疗方法
Acta Pharm Sin B. 2025 Jun;15(6):2930-2944. doi: 10.1016/j.apsb.2025.04.029. Epub 2025 May 5.
2
A systemic review on leptin's role in defining cancer: special emphasis on immunomodulation, inflammation, and therapeutic interventions.关于瘦素在癌症定义中的作用的系统评价：特别强调免疫调节、炎症和治疗干预。
Genes Immun. 2025 May 15. doi: 10.1038/s41435-025-00333-7.
3
IL-1β in Neoplastic Disease and the Role of Its Tumor-Derived Form in the Progression and Treatment of Metastatic Prostate Cancer.

本文引用的文献

1
Molecular mechanisms of leptin and adiponectin in breast cancer.瘦素和脂联素在乳腺癌中的分子机制。
Eur J Cancer. 2011 Jan;47(1):33-43. doi: 10.1016/j.ejca.2010.09.005.
2
Leptin upregulates VEGF in breast cancer via canonic and non-canonical signalling pathways and NFkappaB/HIF-1alpha activation.瘦素通过经典和非经典信号通路以及 NFkappaB/HIF-1alpha 激活上调乳腺癌中的 VEGF。
Cell Signal. 2010 Sep;22(9):1350-62. doi: 10.1016/j.cellsig.2010.05.003. Epub 2010 May 11.
3
Vascular endothelial growth factor receptor-2 in breast cancer.
肿瘤性疾病中的白细胞介素-1β及其肿瘤衍生形式在转移性前列腺癌进展和治疗中的作用。
Cancers (Basel). 2025 Jan 17;17(2):290. doi: 10.3390/cancers17020290.
4
Obesity and leptin in breast cancer angiogenesis.肥胖与乳腺癌血管生成中的瘦素。
Front Endocrinol (Lausanne). 2024 Oct 8;15:1465727. doi: 10.3389/fendo.2024.1465727. eCollection 2024.
5
Obesity-Associated Breast Cancer: Analysis of Risk Factors and Current Clinical Evaluation.肥胖相关性乳腺癌：危险因素分析与临床评估现状。
Adv Exp Med Biol. 2024;1460:767-819. doi: 10.1007/978-3-031-63657-8_26.
6
Next-Cell Hypothesis: Mechanism of Obesity-Associated Carcinogenesis.下一代细胞假说：肥胖相关致癌机制。
Adv Exp Med Biol. 2024;1460:727-766. doi: 10.1007/978-3-031-63657-8_25.
7
Novel Anti-Cancer Stem Cell Compounds: A Comprehensive Review.新型抗癌干细胞化合物：全面综述
Pharmaceutics. 2024 Aug 1;16(8):1024. doi: 10.3390/pharmaceutics16081024.
8
Role of Leptin and Adiponectin in Carcinogenesis.瘦素和脂联素在致癌作用中的作用。
Cancers (Basel). 2023 Aug 24;15(17):4250. doi: 10.3390/cancers15174250.
9
Recent Advances in the Knowledge of the Mechanisms of Leptin Physiology and Actions in Neurological and Metabolic Pathologies.瘦素生理学及其在神经和代谢病理中的作用机制的最新进展。
Int J Mol Sci. 2023 Jan 11;24(2):1422. doi: 10.3390/ijms24021422.
10
Cardiac rehabilitation may influence leptin and VEGF A crosstalk in patients after acute coronary syndrome.心脏康复可能会影响急性冠状动脉综合征患者的瘦素和 VEGF A 相互作用。
Sci Rep. 2022 Jul 12;12(1):11825. doi: 10.1038/s41598-022-16053-1.
乳腺癌中的血管内皮生长因子受体-2
Biochim Biophys Acta. 2010 Aug;1806(1):108-21. doi: 10.1016/j.bbcan.2010.04.004. Epub 2010 May 11.
4
Leptin as a potential therapeutic target for breast cancer prevention and treatment.瘦素作为预防和治疗乳腺癌的潜在治疗靶点。
Expert Opin Ther Targets. 2010 Apr;14(4):443-51. doi: 10.1517/14728221003716466.
5
Effects of IL-1 molecules on growth patterns of 3-MCA-induced cell lines: an interplay between immunogenicity and invasive potential.白细胞介素-1 分子对 3-MCA 诱导细胞系生长模式的影响：免疫原性和侵袭潜能之间的相互作用。
J Immunotoxicol. 2010 Mar;7(1):27-38. doi: 10.3109/15476910903405528.
6
An insertion/deletion polymorphism at miRNA-122-binding site in the interleukin-1alpha 3' untranslated region confers risk for hepatocellular carcinoma.miRNA-122 结合位点插入/缺失多态性与白细胞介素-1α 3'非翻译区易感性相关，导致肝细胞癌。
Carcinogenesis. 2009 Dec;30(12):2064-9. doi: 10.1093/carcin/bgp283.
7
The role of macrophage-derived IL-1 in induction and maintenance of angiogenesis.巨噬细胞衍生的白细胞介素-1在血管生成诱导和维持中的作用。
J Immunol. 2009 Oct 1;183(7):4705-14. doi: 10.4049/jimmunol.0901511. Epub 2009 Sep 14.
8
TGF-beta induces fibroblast activation protein expression; fibroblast activation protein expression increases the proliferation, adhesion, and migration of HO-8910PM [corrected].转化生长因子-β诱导成纤维细胞活化蛋白表达；成纤维细胞活化蛋白表达增加HO-8910PM的增殖、黏附和迁移[校正后] 。
Exp Mol Pathol. 2009 Dec;87(3):189-94. doi: 10.1016/j.yexmp.2009.09.001. Epub 2009 Sep 10.
9
Common genetic variations in the LEP and LEPR genes, obesity and breast cancer incidence and survival.LEP 和 LEPR 基因中的常见遗传变异、肥胖与乳腺癌的发病和生存。
Breast Cancer Res Treat. 2010 Apr;120(3):745-52. doi: 10.1007/s10549-009-0503-1. Epub 2009 Aug 21.
10
Leptin-signaling inhibition results in efficient anti-tumor activity in estrogen receptor positive or negative breast cancer.瘦素信号抑制导致雌激素受体阳性或阴性乳腺癌的有效抗肿瘤活性。
Breast Cancer Res. 2009;11(3):R36. doi: 10.1186/bcr2321. Epub 2009 Jun 16.