• 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

反应性腹膜间皮细胞与肿瘤细胞通过细胞外囊泡的相互作用促进结直肠癌播散。

The Interaction between Reactive Peritoneal Mesothelial Cells and Tumor Cells via Extracellular Vesicles Facilitates Colorectal Cancer Dissemination.

作者信息

Serratì Simona, Porcelli Letizia, Fragassi Francesco, Garofoli Marianna, Di Fonte Roberta, Fucci Livia, Iacobazzi Rosa Maria, Palazzo Antonio, Margheri Francesca, Cristiani Grazia, Albano Anna, De Luca Raffaele, Altomare Donato Francesco, Simone Michele, Azzariti Amalia

机构信息

Laboratory of Nanotechnology, IRCCS Istituto Tumori Giovanni Paolo II, 70124 Bari, Italy.

Laboratory of Experimental Pharmacology, IRCCS Istituto Tumori Giovanni Paolo II, Viale O. Flacco 65, 70124 Bari, Italy.

出版信息

Cancers (Basel). 2021 May 20;13(10):2505. doi: 10.3390/cancers13102505.

DOI:10.3390/cancers13102505
PMID:34065529
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8161093/
Abstract

Advanced colorectal cancer (CRC) is highly metastatic and often results in peritoneal dissemination. The extracellular vesicles (EVs) released by cancer cells in the microenvironment are important mediators of tumor metastasis. We investigated the contribution of EV-mediated interaction between peritoneal mesothelial cells (MCs) and CRC cells in generating a pro-metastatic environment in the peritoneal cavity. Peritoneal MCs isolated from peritoneal lavage fluids displayed high CD44 expression, substantial mesothelial-to-mesenchymal transition (MMT) and released EVs that both directed tumor invasion and caused reprogramming of secretory profiles by increasing TGF-β1 and uPA/uPAR expression and MMP-2/9 activation in tumor cells. Notably, the EVs released by tumor cells induced apoptosis by activating caspase-3, peritoneal MC senescence, and MMT, thereby augmenting the tumor-promoting potential of these cells in the peritoneal cavity. By using pantoprazole, we reduced the biogenesis of EVs and their pro-tumor functions. In conclusion, our findings provided evidence of underlying mechanisms of CRC dissemination driven by the interaction of peritoneal MCs and tumor cells via the EVs released in the peritoneal cavity, which may have important implications for the clinical management of patients.

摘要

晚期结直肠癌（CRC）具有高度转移性，常导致腹膜播散。微环境中癌细胞释放的细胞外囊泡（EVs）是肿瘤转移的重要介质。我们研究了EV介导的腹膜间皮细胞（MCs）与CRC细胞之间的相互作用在腹膜腔中产生促转移环境的作用。从腹腔灌洗液中分离出的腹膜MCs表现出高CD44表达、大量的间皮-间充质转化（MMT），并释放出既能引导肿瘤侵袭又能通过增加肿瘤细胞中TGF-β1和uPA/uPAR表达以及MMP-2/9激活来引起分泌谱重编程的EVs。值得注意的是，肿瘤细胞释放的EVs通过激活caspase-3诱导细胞凋亡、导致腹膜MCs衰老和MMT，从而增强了这些细胞在腹膜腔中的促肿瘤潜能。通过使用泮托拉唑，我们减少了EVs的生物发生及其促肿瘤功能。总之，我们的研究结果为腹膜MCs与肿瘤细胞通过腹膜腔中释放的EVs相互作用驱动CRC播散的潜在机制提供了证据，这可能对患者的临床管理具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5be1/8161093/5d74522117e8/cancers-13-02505-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5be1/8161093/dc1fb62368ae/cancers-13-02505-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5be1/8161093/143bab0c7d94/cancers-13-02505-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5be1/8161093/a9f36ab2ca75/cancers-13-02505-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5be1/8161093/3b1818eb69ce/cancers-13-02505-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5be1/8161093/e23f0f0406ee/cancers-13-02505-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5be1/8161093/b346bd01871b/cancers-13-02505-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5be1/8161093/a278b12d87ff/cancers-13-02505-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5be1/8161093/5d74522117e8/cancers-13-02505-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5be1/8161093/dc1fb62368ae/cancers-13-02505-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5be1/8161093/143bab0c7d94/cancers-13-02505-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5be1/8161093/a9f36ab2ca75/cancers-13-02505-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5be1/8161093/3b1818eb69ce/cancers-13-02505-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5be1/8161093/e23f0f0406ee/cancers-13-02505-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5be1/8161093/b346bd01871b/cancers-13-02505-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5be1/8161093/a278b12d87ff/cancers-13-02505-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5be1/8161093/5d74522117e8/cancers-13-02505-g008.jpg

相似文献

1
The Interaction between Reactive Peritoneal Mesothelial Cells and Tumor Cells via Extracellular Vesicles Facilitates Colorectal Cancer Dissemination.反应性腹膜间皮细胞与肿瘤细胞通过细胞外囊泡的相互作用促进结直肠癌播散。
Cancers (Basel). 2021 May 20;13(10):2505. doi: 10.3390/cancers13102505.
2
Carcinoma-associated fibroblasts derive from mesothelial cells via mesothelial-to-mesenchymal transition in peritoneal metastasis.癌相关成纤维细胞通过腹膜转移中的间皮细胞向间充质转化而来。
J Pathol. 2013 Dec;231(4):517-31. doi: 10.1002/path.4281.
3
Clinicopathological significance of microRNA-21 in extracellular vesicles of pleural lavage fluid of lung adenocarcinoma and its functions inducing the mesothelial to mesenchymal transition.微小RNA-21在肺腺癌胸腔灌洗液细胞外囊泡中的临床病理意义及其诱导间皮-间质转化的功能
Cancer Med. 2020 Apr;9(8):2879-2890. doi: 10.1002/cam4.2928. Epub 2020 Feb 24.
4
LncRNA SPOCD1-AS from ovarian cancer extracellular vesicles remodels mesothelial cells to promote peritoneal metastasis via interacting with G3BP1.卵巢癌细胞外囊泡中的长链非编码RNA SPOCD1-AS通过与G3BP1相互作用重塑间皮细胞，促进腹膜转移。
J Exp Clin Cancer Res. 2021 Mar 16;40(1):101. doi: 10.1186/s13046-021-01899-6.
5
Mesothelial-to-mesenchymal transition as a possible therapeutic target in peritoneal metastasis of ovarian cancer.间皮-间充质转化作为卵巢癌腹膜转移的潜在治疗靶点
J Pathol. 2017 Jun;242(2):140-151. doi: 10.1002/path.4889. Epub 2017 Apr 3.
6
Reprogramming of Mesothelial-Mesenchymal Transition in Chronic Peritoneal Diseases by Estrogen Receptor Modulation and TGF-β1 Inhibition.通过雌激素受体调节和 TGF-β1 抑制重编程慢性腹膜疾病中的间皮-间质转化。
Int J Mol Sci. 2020 Jun 10;21(11):4158. doi: 10.3390/ijms21114158.
7
Mesothelial-to-Mesenchymal Transition Contributes to the Generation of Carcinoma-Associated Fibroblasts in Locally Advanced Primary Colorectal Carcinomas.间皮-间充质转化促进局部晚期原发性结直肠癌中癌相关成纤维细胞的产生。
Cancers (Basel). 2020 Feb 21;12(2):499. doi: 10.3390/cancers12020499.
8
Immune Reprogramming Precision Photodynamic Therapy of Peritoneal Metastasis by Scalable Stem-Cell-Derived Extracellular Vesicles.通过可扩展的干细胞衍生细胞外囊泡对腹膜转移进行免疫重编程精准光动力治疗。
ACS Nano. 2021 Feb 23;15(2):3251-3263. doi: 10.1021/acsnano.0c09938. Epub 2021 Jan 22.
9
Malignant extracellular vesicles carrying MMP1 mRNA facilitate peritoneal dissemination in ovarian cancer.携带 MMP1 mRNA 的恶性细胞外囊泡促进卵巢癌腹膜扩散。
Nat Commun. 2017 Mar 6;8:14470. doi: 10.1038/ncomms14470.
10
The role of the peritoneal microenvironment in the pathogenesis of colorectal peritoneal carcinomatosis.腹膜微环境在结直肠腹膜转移发病机制中的作用。
Exp Mol Pathol. 2020 Aug;115:104442. doi: 10.1016/j.yexmp.2020.104442. Epub 2020 Apr 17.

引用本文的文献

1
Irisin and Metastatic Melanoma: Selective Anti-Invasiveness Activity in BRAF Wild-Type Cells.鸢尾素与转移性黑色素瘤：在BRAF野生型细胞中的选择性抗侵袭活性
Int J Mol Sci. 2025 Jan 14;26(2):652. doi: 10.3390/ijms26020652.
2
Small-Cell Lung Cancer: Is Liquid Biopsy a New Tool Able to Predict the Efficacy of Immunotherapy?小细胞肺癌：液体活检能否成为预测免疫治疗疗效的新工具？
Biomolecules. 2024 Mar 25;14(4):396. doi: 10.3390/biom14040396.
3
Circulating extracellular vesicles are monitoring biomarkers of anti-PD1 response and enhancer of tumor progression and immunosuppression in metastatic melanoma.

本文引用的文献

1
The influence of secreted factors and extracellular vesicles in ovarian cancer metastasis.分泌因子和细胞外囊泡在卵巢癌转移中的作用
EJC Suppl. 2020 Aug 22;15:38-48. doi: 10.1016/j.ejcsup.2019.09.001. eCollection 2020 Aug.
2
uPAR-expressing melanoma exosomes promote angiogenesis by VE-Cadherin, EGFR and uPAR overexpression and rise of ERK1,2 signaling in endothelial cells.uPAR 表达的黑色素瘤外泌体通过 VE-钙黏蛋白、EGFR 和 uPAR 的过表达以及内皮细胞中 ERK1、2 信号通路的升高促进血管生成。
Cell Mol Life Sci. 2021 Mar;78(6):3057-3072. doi: 10.1007/s00018-020-03707-4. Epub 2020 Nov 25.
3
Active notch protects MAPK activated melanoma cell lines from MEK inhibitor cobimetinib.
循环细胞外囊泡是监测抗 PD1 反应和促进转移性黑色素瘤进展和免疫抑制的生物标志物。
J Exp Clin Cancer Res. 2023 Sep 28;42(1):251. doi: 10.1186/s13046-023-02808-9.
4
Exosomes as a Source of Biomarkers for Gastrointestinal Cancers.外泌体作为胃肠道癌症生物标志物的来源
Cancers (Basel). 2023 Feb 16;15(4):1263. doi: 10.3390/cancers15041263.
5
Role of Peritoneal Mesothelial Cells in the Progression of Peritoneal Metastases.腹膜间皮细胞在腹膜转移进展中的作用
Cancers (Basel). 2022 Jun 9;14(12):2856. doi: 10.3390/cancers14122856.
6
Mechanobiology of Colorectal Cancer.结直肠癌的力学生物学
Cancers (Basel). 2022 Apr 12;14(8):1945. doi: 10.3390/cancers14081945.
7
Circulating extracellular vesicles expressing PD1 and PD-L1 predict response and mediate resistance to checkpoint inhibitors immunotherapy in metastatic melanoma.循环细胞外囊泡表达 PD1 和 PD-L1 可预测转移性黑色素瘤对检查点抑制剂免疫治疗的反应并介导耐药性。
Mol Cancer. 2022 Jan 18;21(1):20. doi: 10.1186/s12943-021-01490-9.
8
Salting-Out Approach Is Worthy of Comparison with Ultracentrifugation for Extracellular Vesicle Isolation from Tumor and Healthy Models.盐析法值得与超速离心法比较，用于从肿瘤和健康模型中分离细胞外囊泡。
Biomolecules. 2021 Dec 10;11(12):1857. doi: 10.3390/biom11121857.
9
Mesothelial-to-Mesenchymal Transition and Exosomes in Peritoneal Metastasis of Ovarian Cancer.间皮细胞向间充质转化与卵巢癌腹膜转移中的外泌体。
Int J Mol Sci. 2021 Oct 25;22(21):11496. doi: 10.3390/ijms222111496.
10
Cellular Integrin α5β1 and Exosomal ADAM17 Mediate the Binding and Uptake of Exosomes Produced by Colorectal Carcinoma Cells.细胞整合素 α5β1 和外泌体 ADAM17 介导结直肠癌细胞来源的外泌体的结合和摄取。
Int J Mol Sci. 2021 Sep 14;22(18):9938. doi: 10.3390/ijms22189938.
活性突环可保护 MAPK 激活的黑色素瘤细胞系免受 MEK 抑制剂 cobimetinib 的影响。
Biomed Pharmacother. 2021 Jan;133:111006. doi: 10.1016/j.biopha.2020.111006. Epub 2020 Nov 14.
4
Tomatine Displays Antitumor Potential in In Vitro Models of Metastatic Melanoma.番茄红素在转移性黑色素瘤的体外模型中显示出抗肿瘤潜力。
Int J Mol Sci. 2020 Jul 23;21(15):5243. doi: 10.3390/ijms21155243.
5
The β-adrenergic receptor antagonist propranolol offsets resistance mechanisms to chemotherapeutics in diverse sarcoma subtypes: a pilot study.β-肾上腺素能受体拮抗剂普萘洛尔抵消了不同肉瘤亚型对化疗药物的耐药机制：一项初步研究。
Sci Rep. 2020 Jun 26;10(1):10465. doi: 10.1038/s41598-020-67342-6.
6
Understanding oncogenicity of cancer driver genes and mutations in the cancer genomics era.在癌症基因组学时代，了解致癌基因和突变的致癌性。
FEBS Lett. 2020 Dec;594(24):4233-4246. doi: 10.1002/1873-3468.13781. Epub 2020 Apr 28.
7
Mesothelial-to-Mesenchymal Transition Contributes to the Generation of Carcinoma-Associated Fibroblasts in Locally Advanced Primary Colorectal Carcinomas.间皮-间充质转化促进局部晚期原发性结直肠癌中癌相关成纤维细胞的产生。
Cancers (Basel). 2020 Feb 21;12(2):499. doi: 10.3390/cancers12020499.
8
Adaptive mutability of colorectal cancers in response to targeted therapies.结直肠癌对靶向治疗的适应性突变。
Science. 2019 Dec 20;366(6472):1473-1480. doi: 10.1126/science.aav4474. Epub 2019 Nov 7.
9
Mechanisms of Metastasis in Colorectal Cancer and Metastatic Organotropism: Hematogenous versus Peritoneal Spread.结直肠癌转移机制及转移器官嗜性：血行转移与腹膜播散
J Oncol. 2019 Sep 19;2019:7407190. doi: 10.1155/2019/7407190. eCollection 2019.
10
Exosomes promote pre-metastatic niche formation in ovarian cancer.外泌体促进卵巢癌转移前生态位形成。
Mol Cancer. 2019 Aug 13;18(1):124. doi: 10.1186/s12943-019-1049-4.