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药理学抑制衔接蛋白 PDZ2 结构域会损害乳腺癌细胞的活性，并减少外泌体中 syndecan 和 EpCAM 货物的装载。

Pharmacological inhibition of syntenin PDZ2 domain impairs breast cancer cell activities and exosome loading with syndecan and EpCAM cargo.

机构信息

Equipe labellisée Ligue 2018 Centre de Recherche en Cancérologie de Marseille (CRCM) Aix-Marseille Université, Inserm, CNRS, Institut Paoli-Calmettes Marseille France.

Centre de Recherche en Cancérologie de Marseille Integrative Structural & Chemical Biology Aix-Marseille Université, Inserm, CNRS, Institut Paoli Calmettes Marseille France.

出版信息

J Extracell Vesicles. 2020 Dec;10(2):e12039. doi: 10.1002/jev2.12039. Epub 2020 Dec 15.

DOI:10.1002/jev2.12039
PMID:33343836
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7737769/
Abstract

Exosomes support cell-to-cell communication in physiology and disease, including cancer. We currently lack tools, such as small chemicals, capable of modifying exosome composition and activity in a specific manner. Building on our previous understanding of how syntenin, and its PDZ partner syndecan (SDC), impact on exosome composition we optimized a small chemical compound targeting the PDZ2 domain of syntenin. In vitro , in tests on MCF-7 breast carcinoma cells, this compound is non-toxic and impairs cell proliferation, migration and primary sphere formation. It does not affect the size or the number of secreted particles, yet it decreases the amounts of exosomal syntenin, ALIX and SDC4 while leaving other exosomal markers unaffected. Interestingly, it also blocks the sorting of EpCAM, a target used for carcinoma exosome immunocapture. Our study highlights the first characterization of a small pharmacological inhibitor of the syntenin-exosomal pathway, of potential interest for exosome research and oncology.

摘要

外泌体在生理和疾病（包括癌症）中支持细胞间通讯。我们目前缺乏能够以特定方式修饰外泌体组成和活性的工具，如小分子化学物质。基于我们之前对 syntenin 及其 PDZ 伙伴 syndecan (SDC) 如何影响外泌体组成的理解，我们优化了一种针对 syntenin PDZ2 结构域的小分子化合物。在 MCF-7 乳腺癌细胞的体外试验中，该化合物无毒，可损害细胞增殖、迁移和初级球体形成。它不影响分泌颗粒的大小或数量，但会减少外泌体 syntenin、ALIX 和 SDC4 的含量，而其他外泌体标志物不受影响。有趣的是，它还阻止了 EpCAM 的分选，EpCAM 是用于癌外泌体免疫捕获的靶标。我们的研究首次描述了一种 syntenin-外泌体途径的小分子药理学抑制剂，该抑制剂可能对外泌体研究和肿瘤学具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcee/7737769/94695246492c/JEV2-10-e12039-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcee/7737769/445f7e90b0b0/JEV2-10-e12039-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcee/7737769/f7b83c436840/JEV2-10-e12039-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcee/7737769/d80bf77fe903/JEV2-10-e12039-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcee/7737769/b46f40fddcf4/JEV2-10-e12039-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcee/7737769/3634aa1ca445/JEV2-10-e12039-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcee/7737769/94695246492c/JEV2-10-e12039-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcee/7737769/445f7e90b0b0/JEV2-10-e12039-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcee/7737769/f7b83c436840/JEV2-10-e12039-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcee/7737769/d80bf77fe903/JEV2-10-e12039-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcee/7737769/b46f40fddcf4/JEV2-10-e12039-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcee/7737769/3634aa1ca445/JEV2-10-e12039-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcee/7737769/94695246492c/JEV2-10-e12039-g006.jpg

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