2. Academic Validation
  3. Apoptotic Extracellular Vesicles Ameliorate Multiple Myeloma by Restoring Fas-Mediated Apoptosis

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

  • ACS Nano. 2021 Sep 28;15(9):14360-14372. doi: 10.1021/acsnano.1c03517.
Juan Wang 1,  Zeyuan Cao 1,  Panpan Wang 1,  Xiao Zhang 1 2,  Jianxia Tang 1 3,  Yifan He 1,  Zhiqing Huang 1,  Xueli Mao 1,  Songtao Shi 1 4 5,  Xiaoxing Kou 1 4 5
Affiliations

Affiliations

  • 1 South China Center of Craniofacial Stem Cell Research, Hospital of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou 510080, China.
  • 2 Department of Prosthodontics, Peking University School and Hospital of Stomatology and National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital and Material Technology of Stomatology, and Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.
  • 3 Hunan Key Laboratory of Oral Health Research and Hunan Clinical Research Center of Oral Major Diseases and Oral Health, Xiangya School of Stomatology, Xiangya Stomatological Hospital, Central South University, Changsha 410000, China.
  • 4 Department of Anatomy and Cell Biology, University of Pennsylvania, School of Dental Medicine, Philadelphia, Pennsylvania 19104, United States.
  • 5 Key Laboratory of Stem Cells and Tissue Engineering (Sun Yat-Sen University), Ministry of Education, Guangzhou 510080, China.
PMID: 34506129 DOI: 10.1021/acsnano.1c03517
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 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.

Keywords

Fas; FasL; apoptosis; apoptotic extracellular vesicles; multiple myeloma.

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