• 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

癌细胞分泌的 IGF2 可促使成纤维细胞和骨髓来源的血管祖细胞促进肿瘤进展。

Cancer cell-secreted IGF2 instigates fibroblasts and bone marrow-derived vascular progenitor cells to promote cancer progression.

机构信息

School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, 21 Sassoon Road, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.

The University of Hong Kong-Shenzhen Institute of Research and Innovation (HKU-SIRI), Kejizhong 2nd Rd., Hi-Tech Industrial Park, Nanshan District, Shenzhen 518057, China.

出版信息

Nat Commun. 2017 Feb 10;8:14399. doi: 10.1038/ncomms14399.

DOI:10.1038/ncomms14399
PMID:28186102
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5309924/
Abstract

Local interactions between cancer cells and stroma can produce systemic effects on distant organs to govern cancer progression. Here we show that IGF2 secreted by inhibitor of differentiation (Id1)-overexpressing oesophageal cancer cells instigates VEGFR1-positive bone marrow cells in the tumour macroenvironment to form pre-metastatic niches at distant sites by increasing VEGF secretion from cancer-associated fibroblasts. Cancer cells are then attracted to the metastatic site via the CXCL5/CXCR2 axis. Bone marrow cells transplanted from nude mice bearing Id1-overexpressing oesophageal tumours enhance tumour growth and metastasis in recipient mice, whereas systemic administration of VEGFR1 antibody abrogates these effects. Mechanistically, IGF2 regulates VEGF in fibroblasts via miR-29c in a p53-dependent manner. Analysis of patient serum samples showed that concurrent elevation of IGF2 and VEGF levels may serve as a prognostic biomarker for oesophageal cancer. These findings suggest that the Id1/IGF2/VEGF/VEGFR1 cascade plays a critical role in tumour-driven pathophysiological processes underlying cancer progression.

摘要

癌细胞与基质之间的局部相互作用可以对远处器官产生全身性影响，从而控制癌症的进展。在这里，我们表明，Id1 过表达的食管癌细胞分泌的 IGF2 通过增加癌相关成纤维细胞中 VEGF 的分泌，促使肿瘤微环境中的 VEGFR1 阳性骨髓细胞在远处部位形成前转移龛。然后，癌细胞通过 CXCL5/CXCR2 轴被吸引到转移部位。从携带 Id1 过表达的食管癌肿瘤的裸鼠中移植的骨髓细胞增强了受体小鼠的肿瘤生长和转移，而 VEGFR1 抗体的全身给药则消除了这些作用。从机制上讲，IGF2 通过 p53 依赖性方式在成纤维细胞中调节 miR-29c 进而调节 VEGF。对患者血清样本的分析表明，IGF2 和 VEGF 水平的同时升高可能是食管癌的预后生物标志物。这些发现表明，Id1/IGF2/VEGF/VEGFR1 级联在肿瘤驱动的癌症进展相关病理生理过程中起着关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/263d/5309924/da5f8f4a0dd6/ncomms14399-f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/263d/5309924/cf2ea76dae45/ncomms14399-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/263d/5309924/1e9a697b8c0b/ncomms14399-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/263d/5309924/acc254702736/ncomms14399-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/263d/5309924/15ad678fc5de/ncomms14399-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/263d/5309924/d57135746fec/ncomms14399-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/263d/5309924/94300d1ff7fe/ncomms14399-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/263d/5309924/2a0e207e1038/ncomms14399-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/263d/5309924/7d17dd8ee646/ncomms14399-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/263d/5309924/da5f8f4a0dd6/ncomms14399-f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/263d/5309924/cf2ea76dae45/ncomms14399-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/263d/5309924/1e9a697b8c0b/ncomms14399-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/263d/5309924/acc254702736/ncomms14399-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/263d/5309924/15ad678fc5de/ncomms14399-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/263d/5309924/d57135746fec/ncomms14399-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/263d/5309924/94300d1ff7fe/ncomms14399-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/263d/5309924/2a0e207e1038/ncomms14399-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/263d/5309924/7d17dd8ee646/ncomms14399-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/263d/5309924/da5f8f4a0dd6/ncomms14399-f9.jpg

相似文献

1
Cancer cell-secreted IGF2 instigates fibroblasts and bone marrow-derived vascular progenitor cells to promote cancer progression.癌细胞分泌的 IGF2 可促使成纤维细胞和骨髓来源的血管祖细胞促进肿瘤进展。
Nat Commun. 2017 Feb 10;8:14399. doi: 10.1038/ncomms14399.
2
Id1-induced IGF-II and its autocrine/endocrine promotion of esophageal cancer progression and chemoresistance--implications for IGF-II and IGF-IR-targeted therapy.Id1 诱导的 IGF-II 及其自分泌/内分泌促进食管癌的进展和化疗耐药——对 IGF-II 和 IGF-IR 靶向治疗的影响。
Clin Cancer Res. 2014 May 15;20(10):2651-62. doi: 10.1158/1078-0432.CCR-13-2735. Epub 2014 Mar 5.
3
Competitive Binding Between Id1 and E2F1 to Cdc20 Regulates E2F1 Degradation and Thymidylate Synthase Expression to Promote Esophageal Cancer Chemoresistance.Id1与E2F1对Cdc20的竞争性结合调节E2F1降解及胸苷酸合成酶表达以促进食管癌化疗耐药
Clin Cancer Res. 2016 Mar 1;22(5):1243-55. doi: 10.1158/1078-0432.CCR-15-1196. Epub 2015 Oct 16.
4
Addiction to the IGF2-ID1-IGF2 circuit for maintenance of the breast cancer stem-like cells.对维持乳腺癌干细胞样细胞的IGF2-ID1-IGF2回路成瘾。
Oncogene. 2017 Mar 2;36(9):1276-1286. doi: 10.1038/onc.2016.293. Epub 2016 Aug 22.
5
IGF2 induces CD133 expression in esophageal cancer cells to promote cancer stemness.IGF2 诱导食管癌细胞中 CD133 的表达，促进肿瘤干细胞特性。
Cancer Lett. 2018 Jul 1;425:88-100. doi: 10.1016/j.canlet.2018.03.039. Epub 2018 Mar 29.
6
Interaction between IGF2-PI3K axis and cancer-associated-fibroblasts promotes anal squamous carcinogenesis.IGF2-PI3K 轴与癌症相关成纤维细胞的相互作用促进肛门鳞癌的发生。
Int J Cancer. 2019 Oct 1;145(7):1852-1859. doi: 10.1002/ijc.32178. Epub 2019 Feb 18.
7
PA28γ coordinates the cross-talk between cancer-associated fibroblasts and tumor cells to promote OSCC progression via HDAC1/E2F3/IGF2 signaling.PA28γ 通过 HDAC1/E2F3/IGF2 信号促进肿瘤相关成纤维细胞与肿瘤细胞间的串扰来促进口腔鳞状细胞癌的进展。
Cancer Lett. 2024 Jul 10;594:216962. doi: 10.1016/j.canlet.2024.216962. Epub 2024 May 18.
8
Long non-coding RNA 91H contributes to the occurrence and progression of esophageal squamous cell carcinoma by inhibiting IGF2 expression.长链非编码RNA 91H通过抑制IGF2表达促进食管鳞状细胞癌的发生和发展。
Mol Carcinog. 2015 May;54(5):359-67. doi: 10.1002/mc.22106. Epub 2014 Apr 7.
9
Stromal-derived IGF2 promotes colon cancer progression via paracrine and autocrine mechanisms.基质来源的胰岛素样生长因子2通过旁分泌和自分泌机制促进结肠癌进展。
Oncogene. 2017 Sep 21;36(38):5341-5355. doi: 10.1038/onc.2017.116. Epub 2017 May 22.
10
The crucial role of miR-126 on suppressing progression of esophageal cancer by targeting VEGF-A.miR-126通过靶向VEGF-A在抑制食管癌进展中的关键作用。
Cell Mol Biol Lett. 2016 Jul 28;21:3. doi: 10.1186/s11658-016-0004-2. eCollection 2016.

引用本文的文献

1
The role of IGF-2 and its variants in enhancing endothelial migration and angiogenesis.胰岛素样生长因子-2（IGF-2）及其变体在促进内皮细胞迁移和血管生成中的作用。
Front Cell Dev Biol. 2025 May 16;13:1598705. doi: 10.3389/fcell.2025.1598705. eCollection 2025.
2
Integration of single-nuclei and spatial transcriptomics to decipher tumor phenotype predictive of relapse-free survival in Wilms tumor.整合单核与空间转录组学以解读预测肾母细胞瘤无复发生存的肿瘤表型。
Front Immunol. 2025 Mar 3;16:1539897. doi: 10.3389/fimmu.2025.1539897. eCollection 2025.
3
Reprogramming of fibroblasts into cancer-associated fibroblasts via IGF2-mediated autophagy promotes metastasis of lung cancer cells.

本文引用的文献

1
MiR-29c regulates the expression of miR-34c and miR-449a by targeting DNA methyltransferase 3a and 3b in nasopharyngeal carcinoma.在鼻咽癌中，miR-29c通过靶向DNA甲基转移酶3a和3b来调控miR-34c和miR-449a的表达。
BMC Cancer. 2016 Mar 15;16:218. doi: 10.1186/s12885-016-2253-x.
2
Tumour cell-derived Wnt7a recruits and activates fibroblasts to promote tumour aggressiveness.肿瘤细胞衍生的Wnt7a招募并激活成纤维细胞以促进肿瘤侵袭性。
Nat Commun. 2016 Jan 18;7:10305. doi: 10.1038/ncomms10305.
3
Competitive Binding Between Id1 and E2F1 to Cdc20 Regulates E2F1 Degradation and Thymidylate Synthase Expression to Promote Esophageal Cancer Chemoresistance.
通过IGF2介导的自噬将成纤维细胞重编程为癌症相关成纤维细胞可促进肺癌细胞转移。
iScience. 2024 Oct 28;27(12):111269. doi: 10.1016/j.isci.2024.111269. eCollection 2024 Dec 20.
4
Spatial analyses revealed CXCL5 and SLC6A14 as the markers of microvascular invasion in intrahepatic cholangiocarcinoma.空间分析显示，CXCL5和SLC6A14是肝内胆管癌微血管侵犯的标志物。
Hepatol Commun. 2024 Dec 11;9(1). doi: 10.1097/HC9.0000000000000597. eCollection 2025 Jan 1.
5
Biomarkers of lymph node metastasis in esophageal cancer.食管癌淋巴结转移的生物标志物。
Front Immunol. 2024 Sep 27;15:1457612. doi: 10.3389/fimmu.2024.1457612. eCollection 2024.
6
The role of transcription factors in the crosstalk between cancer-associated fibroblasts and tumor cells.转录因子在癌症相关成纤维细胞与肿瘤细胞间串扰中的作用。
J Adv Res. 2025 Jan;67:121-132. doi: 10.1016/j.jare.2024.01.033. Epub 2024 Feb 2.
7
KCTD4 interacts with CLIC1 to disrupt calcium homeostasis and promote metastasis in esophageal cancer.KCTD4与CLIC1相互作用，破坏钙稳态并促进食管癌转移。
Acta Pharm Sin B. 2023 Oct;13(10):4217-4233. doi: 10.1016/j.apsb.2023.07.013. Epub 2023 Jul 17.
8
The tobacco-specific carcinogen NNK induces pulmonary tumorigenesis via nAChR/Src/STAT3-mediated activation of the renin-angiotensin system and IGF-1R signaling.烟草特异性致癌原 NNK 通过烟碱型乙酰胆碱受体/原癌基因Src/信号转导与转录激活因子 3 介导的肾素-血管紧张素系统和胰岛素样生长因子 1 受体信号通路诱导肺肿瘤发生。
Exp Mol Med. 2023 Jun;55(6):1131-1144. doi: 10.1038/s12276-023-00994-2. Epub 2023 Jun 1.
9
Spatial analysis of stromal signatures identifies invasive front carcinoma-associated fibroblasts as suppressors of anti-tumor immune response in esophageal cancer.肿瘤微环境特征的空间分析鉴定出浸润前缘癌相关成纤维细胞是食管癌抗肿瘤免疫反应的抑制因子。
J Exp Clin Cancer Res. 2023 May 31;42(1):136. doi: 10.1186/s13046-023-02697-y.
10
Reciprocal Regulation of Cancer-Associated Fibroblasts and Tumor Microenvironment in Gastrointestinal Cancer: Implications for Cancer Dormancy.胃肠道癌中癌症相关成纤维细胞与肿瘤微环境的相互调节：对癌症休眠的影响
Cancers (Basel). 2023 Apr 27;15(9):2513. doi: 10.3390/cancers15092513.
Id1与E2F1对Cdc20的竞争性结合调节E2F1降解及胸苷酸合成酶表达以促进食管癌化疗耐药
Clin Cancer Res. 2016 Mar 1;22(5):1243-55. doi: 10.1158/1078-0432.CCR-15-1196. Epub 2015 Oct 16.
4
Id1 suppresses anti-tumour immune responses and promotes tumour progression by impairing myeloid cell maturation.Id1通过损害髓样细胞成熟来抑制抗肿瘤免疫反应并促进肿瘤进展。
Nat Commun. 2015 Apr 29;6:6840. doi: 10.1038/ncomms7840.
5
The tumour-induced systemic environment as a critical regulator of cancer progression and metastasis.肿瘤诱导的全身性环境作为癌症进展和转移的关键调节者。
Nat Cell Biol. 2014 Aug;16(8):717-27. doi: 10.1038/ncb3015.
6
MicroRNA-29c mediates initiation of gastric carcinogenesis by directly targeting ITGB1.MicroRNA-29c 通过直接靶向 ITGB1 介导胃癌的发生。
Gut. 2015 Feb;64(2):203-14. doi: 10.1136/gutjnl-2013-306640. Epub 2014 May 28.
7
Depletion of carcinoma-associated fibroblasts and fibrosis induces immunosuppression and accelerates pancreas cancer with reduced survival.耗竭癌相关成纤维细胞和纤维化会诱导免疫抑制，并加速胰腺癌发展，降低患者生存率。
Cancer Cell. 2014 Jun 16;25(6):719-34. doi: 10.1016/j.ccr.2014.04.005. Epub 2014 May 22.
8
Tumor macroenvironment and metabolism.肿瘤宏观环境与代谢。
Semin Oncol. 2014 Apr;41(2):281-95. doi: 10.1053/j.seminoncol.2014.02.005. Epub 2014 Mar 1.
9
Identification of genomic alterations in oesophageal squamous cell cancer.食管鳞状细胞癌的基因组改变鉴定。
Nature. 2014 May 1;509(7498):91-5. doi: 10.1038/nature13176. Epub 2014 Mar 16.
10
Id1-induced IGF-II and its autocrine/endocrine promotion of esophageal cancer progression and chemoresistance--implications for IGF-II and IGF-IR-targeted therapy.Id1 诱导的 IGF-II 及其自分泌/内分泌促进食管癌的进展和化疗耐药——对 IGF-II 和 IGF-IR 靶向治疗的影响。
Clin Cancer Res. 2014 May 15;20(10):2651-62. doi: 10.1158/1078-0432.CCR-13-2735. Epub 2014 Mar 5.