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希佩尔-林道氏-无脉络膜症相关的癌细胞来源的外泌体促进肾细胞癌转移。

Exosomes from Von Hippel-Lindau-Null Cancer Cells Promote Metastasis in Renal Cell Carcinoma.

机构信息

Department of Bioengineering, University of California, Los Angeles, CA 90095, USA.

Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.

出版信息

Int J Mol Sci. 2023 Dec 9;24(24):17307. doi: 10.3390/ijms242417307.

DOI:10.3390/ijms242417307
PMID:38139136
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10743428/
Abstract

Exosomes are extracellular vesicles that modulate essential physiological and pathological signals. Communication between cancer cells that express the tumor suppressor gene and those that do not is instrumental to distant metastasis in renal cell carcinoma (RCC). In a novel metastasis model, VHL(-) cancer cells are the metastatic driver, while VHL(+) cells receive metastatic signals from VHL(-) cells and undergo aggressive transformation. This study investigates whether exosomes could be mediating metastatic crosstalk. Exosomes isolated from paired VHL(+) and VHL(-) cancer cell lines were assessed for physical, biochemical, and biological characteristics. Compared to the VHL(+) cells, VHL(-) cells produce significantly more exosomes that augment epithelial-to-mesenchymal transition (EMT) and migration of VHL(+) cells. Using a Cre- exosome reporter system, the fluorescent color conversion and migration were correlated with dose-dependent delivery of VHL(-) exosomes. VHL(-) exosomes even induced a complete cascade of distant metastasis when added to VHL(+) tumor xenografts in a duck chorioallantoic membrane (dCAM) model, while (+) exosomes did not. Therefore, this study supports that exosomes from VHL(-) cells could mediate critical cell-to-cell crosstalk to promote metastasis in RCC.

摘要

外泌体是调节重要生理和病理信号的细胞外囊泡。表达肿瘤抑制基因的癌细胞与不表达该基因的癌细胞之间的通讯对于肾细胞癌（RCC）的远处转移至关重要。在一种新型转移模型中，VHL(-)癌细胞是转移的驱动者，而 VHL(+)细胞从 VHL(-)细胞接收转移信号并发生侵袭性转化。本研究探讨了外泌体是否可以介导转移串扰。从配对的 VHL(+)和 VHL(-)癌细胞系中分离出外泌体，评估其物理、生化和生物学特征。与 VHL(+)细胞相比，VHL(-)细胞产生的外泌体明显更多，可增强上皮间质转化（EMT）和 VHL(+)细胞的迁移。使用 Cre-外泌体报告系统，荧光颜色转换和迁移与 VHL(-)外泌体剂量依赖性递呈相关。甚至当将 VHL(-)外泌体添加到 duck chorioallantoic membrane (dCAM) 模型中的 VHL(+)肿瘤异种移植物中时，VHL(-)外泌体也会诱导完整的远处转移级联反应，而 (+)外泌体则不会。因此，本研究支持 VHL(-)细胞的外泌体可以介导关键的细胞间串扰，促进 RCC 的转移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14ec/10743428/44e479ce78f3/ijms-24-17307-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14ec/10743428/39f916eb14ee/ijms-24-17307-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14ec/10743428/c7e3bfda2ef2/ijms-24-17307-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14ec/10743428/c3d775dcaf39/ijms-24-17307-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14ec/10743428/f774e68ae7d7/ijms-24-17307-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14ec/10743428/44e479ce78f3/ijms-24-17307-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14ec/10743428/39f916eb14ee/ijms-24-17307-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14ec/10743428/c7e3bfda2ef2/ijms-24-17307-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14ec/10743428/c3d775dcaf39/ijms-24-17307-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14ec/10743428/f774e68ae7d7/ijms-24-17307-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14ec/10743428/44e479ce78f3/ijms-24-17307-g005.jpg

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本文引用的文献

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