Extracellular vesicles released by glioma cells are decorated by Annexin A2 allowing for cellular uptake via heparan sulfate.

Autor: Song YX; Hunan Provincial Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, Changsha Medical University, Changsha, China.; Department of Neurosurgery, Xiang-Ya Hospital, Central South University, Changsha, China.; Department of Pharmaceutical Engineering, College of Chemistry and Chemical Engineering, Central South University, Changsha, China., Li X; Hunan Provincial Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, Changsha Medical University, Changsha, China. tengyunxin2010@163.com.; Department of Neurosurgery, Xiang-Ya Hospital, Central South University, Changsha, China. tengyunxin2010@163.com.; Department of Pharmaceutical Engineering, College of Chemistry and Chemical Engineering, Central South University, Changsha, China. tengyunxin2010@163.com., Nie SD; Institute of Clinical Medicine, Hunan provincial people's hospital, the first affiliated hospital of Hunan Normal University, Changsha, China., Hu ZX; Department of Neurosurgery, Xiang-Ya Hospital, Central South University, Changsha, China., Zhou D; Department of Pharmaceutical Engineering, College of Chemistry and Chemical Engineering, Central South University, Changsha, China., Sun DY; Department of Pharmaceutical Engineering, College of Chemistry and Chemical Engineering, Central South University, Changsha, China., Zhou GY; Department of Neurology, Brain hospital of Hunan Province, Changsha, China., Wang Y; Department of Pathology, School of Basic Medical Science, Central South University, Changsha, China., Liu JJ; Department of Pharmaceutical Engineering, College of Chemistry and Chemical Engineering, Central South University, Changsha, China., Song T; Department of Neurosurgery, Xiang-Ya Hospital, Central South University, Changsha, China. songtaocsuws@163.com., Wang S; Department of Pharmaceutical Engineering, College of Chemistry and Chemical Engineering, Central South University, Changsha, China. wangshancsu0717@163.com.
Jazyk: angličtina
Zdroj: Cancer gene therapy [Cancer Gene Ther] 2023 Aug; Vol. 30 (8), pp. 1156-1166. Date of Electronic Publication: 2023 May 25.
DOI: 10.1038/s41417-023-00627-w
Abstrakt: Extracellular vesicles (EVs) play a crucial role in regulating cell behavior by delivering their cargo to target cells. However, the mechanisms underlying EV-cell interactions are not well understood. Previous studies have shown that heparan sulfate (HS) on target cell surfaces can act as receptors for exosomes uptake, but the ligand for HS on EVs has not been identified. In this study, we isolated EVs from glioma cell lines and glioma patients and identified Annexin A2 (AnxA2) on EVs as a key HS-binding ligand and mediator of EV-cell interactions. Our findings suggest that HS plays a dual role in EV-cell interactions, where HS on EVs captures AnxA2, and on target cells, it acts as a receptor for AnxA2. Removal of HS from the EV surface inhibits EV-target cell interaction by releasing AnxA2. Furthermore, we found that AnxA2-mediated binding of EVs to vascular endothelial cells promotes angiogenesis, and that antibody against AnxA2 inhibited the ability of glioma-derived EVs to stimulate angiogenesis by reducing the uptake of EVs. Our study also suggests that the AnxA2-HS interaction may accelerate the glioma-derived EVs-mediated angiogenesis and that combining AnxA2 on glioma cells with HS on endothelial cells may effectively improve the prognosis evaluation of glioma patients.
(© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze: MEDLINE
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