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

Wang, Juan, Cao, Zeyuan, Wang, Panpan, Zhang, Xiao, Tang, Jianxia, He, Yifan, Huang, Zhiqing, Mao, Xueli, Shi, Songtao, Kou, Xiaoxing·2021·ACS Nano
DOI 10.1021/acsnano.1c03517
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Abstract

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 Ca 2+ influx and elevation of cytosolic Ca 2+ . 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.

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Metadata

Authors
Wang, J., Cao, Z., Wang, P., Zhang, X., Tang, J., He, Y., Huang, Z., Mao, X., Shi, S., & Kou, X.
Venue
ACS Nano
Publisher
American Chemical Society (ACS)
Published
2021-09-10
Volume
15
Issue
9
Pages
14360-14372
ISSN
  • 1936-0851
  • 1936-086X
DOI
10.1021/acsnano.1c03517
Cited by
122
References
3
Language
en
Licence
creativecommons.org/licenses/by-nc-nd/4.0/ (unspecified)
Funders
  • National Natural Science Foundation of China (81800969)
  • Natural Science Foundation of Guangdong Province (2016A030313262, 2017A030310508)
  • Sun Yat-sen University Young Teacher Key Cultivation Project (18ykzd05)
  • Pearl River Talent Recruitment Program (2019JC01Y182, 2019QN01Y138, 2019ZT08Y485)
  • Youth Teacher Training Project of Sun Yat-sen University (17ykpy72)
  • the National Science and Technology Major Project of the Ministry of Science and Technology of China (2018ZX10302207-001-002)
  • Guangdong Financial Fund for High-Caliber Hospital Construction (174-2018-XMZC-0001-03-0125, D-07, D-11)

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