دورية أكاديمية
The capture of extracellular vesicles endogenously released by xenotransplanted tumours induces an inflammatory reaction in the premetastatic niche
| العنوان: | The capture of extracellular vesicles endogenously released by xenotransplanted tumours induces an inflammatory reaction in the premetastatic niche |
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| المؤلفون: | Blavier, Laurence, Nakata, Rie, Neviani, Paolo, Sharma, Khounish, Shimada, Hiroyuki, Benedicto García, Aitor, Matei, Irina, Lyden, David, DeClerck, Yves A. |
| بيانات النشر: | Wiley |
| سنة النشر: | 2023 |
| المجموعة: | ADDI: Repositorio Institucional de la Universidad del País Vasco / Euskal Herriko Unibertsitatea (UPV/EHU - Basque Country University) |
| مصطلحات موضوعية: | exosomes, extracellular vesicles, inflammation, metastasis, microRNA, pre-metastatic niche, tumour microenvironment |
| الوصف: | The capture of tumour-derived extracellular vesicles (TEVs) by cells in the tumour microenvironment (TME) contributes to metastasis and notably to the formation of the pre-metastatic niche (PMN). However, due to the challenges associated with modelling release of small EVs in vivo, the kinetics of PMN formation in response to endogenously released TEVs have not been examined. Here, we have studied the endogenous release of TEVs in mice orthotopically implanted with metastatic human melanoma (MEL) and neuroblastoma (NB) cells releasing GFP-tagged EVs (GFTEVs) and their capture by host cells to demonstrate the active contribution of TEVs to metastasis. Human GFTEVs captured by mouse macrophages in vitro resulted in transfer of GFP vesicles and the human exosomal miR-1246. Mice orthotopically implanted with MEL or NB cells showed the presence of TEVs in the blood between 5 and 28 days after implantation. Moreover, kinetic analysis of TEV capture by resident cells relative to the arrival and outgrowth of TEV-producing tumour cells in metastatic organs demonstrated that the capture of TEVs by lung and liver cells precedes the homing of metastatic tumour cells, consistent with the critical roles of TEVs in PMN formation. Importantly, TEV capture at future sites of metastasis was associated with the transfer of miR-1246 to lung macrophages, liver macrophages, and stellate cells. This is the first demonstration that the capture of endogenously released TEVs is organotropic as demonstrated by the presence of TEV-capturing cells only in metastatic organs and their absence in non-metastatic organs. The capture of TEVs in the PMN induced dynamic changes in inflammatory gene expression which evolved to a pro-tumorigenic reaction as the niche progressed to the metastatic state. Thus, our work describes a novel approach to TEV tracking in vivo that provides additional insights into their role in the earliest stages of metastatic progression. ; The authors would like to thank Mrs. J. Rosenberg for her help in the formatting of ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2001-3078 |
| العلاقة: | Journal of Extracellular Vesicles 12(5) : (2023) // Article ID 12326; http://hdl.handle.net/10810/61783Test |
| DOI: | 10.1002/jev2.12326 |
| الإتاحة: | https://doi.org/10.1002/jev2.12326Test http://hdl.handle.net/10810/61783Test |
| حقوق: | info:eu-repo/semantics/openAccess ; http://creativecommons.org/licenses/by-nc-nd/3.0/esTest/ ; © 2023 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. ; Atribución-NoComercial-SinDerivadas 3.0 España |
| رقم الانضمام: | edsbas.5329B9B4 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 20013078 |
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| DOI: | 10.1002/jev2.12326 |