Apoptotic Extracellular Vesicles Ameliorate Multiple Myeloma by Restoring Fas-Mediated Apoptosis

Autor:	Jianxia Tang, Xiaoxing Kou, Songtao Shi, Zeyuan Cao, Panpan Wang, Xueli Mao, Xiao Zhang, Juan Wang, Yifan He, Zhiqing Huang
Rok vydání:	2021
Předmět:	Cell growth Chemistry Mesenchymal stem cell Cell General Engineering General Physics and Astronomy Apoptosis Fas ligand Cell biology Cell membrane Extracellular Vesicles Mice Cytosol medicine.anatomical_structure Cancer cell medicine Animals General Materials Science Multiple Myeloma
Zdroj:	ACS Nano. 15:14360-14372
ISSN:	1936-086X 1936-0851
DOI:	10.1021/acsnano.1c03517
Popis:	Apoptosis is critical for maintaining bodily homeostasis and produces a large number of apoptotic extracellular vesicles (apoEVs). Several types of cancer cells display reduced expression of Fas on the cell surface and are thus capable of escaping Fas ligand-induced apoptosis. However, it is unknown whether normal cell-derived apoEVs can regulate tumor growth. In this study, we show that apoEVs can induce multiple myeloma (MM) cell apoptosis and inhibit MM cell growth. Systemic infusion of mesenchymal stem cell (MSC)-derived apoEVs significantly prolongs the lifespan of MM mice. Mechanistically, apoEVs directly contact MM cells to facilitate Fas trafficking from the cytoplasm to the cell membrane by evoking Ca2+ influx and elevation of cytosolic Ca2+. Subsequently, apoEVs use their Fas ligand to activate the Fas pathway in MM cells, leading to the initiation of apoptosis. This study identifies the role of apoEVs in inducing MM apoptosis and suggests a potential for apoEVs to treat MM.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9f11d7a4209d6c31f0317df1ac6df0de https://doi.org/10.1021/acsnano.1c03517 Zobrazit plný text záznamu