Adenosine receptors regulate exosome production

Purinergic signalling

article

Nils Ludwig¹  Juliana H. Azambuja¹  Aparna Rao²  Delbert G. Gillespie⁵  Edwin K. Jackson⁵  Theresa L. Whiteside¹ 

[1] Department of Pathology, University of Pittsburgh School of Medicine;UPMC Hillman Cancer Center;Programa de Pós-Graduação em Biociências, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA);Department of Neurological Surgery, University of Pittsburgh Medical Center;Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine;Department of Immunology, University of Pittsburgh School of Medicine;Department of Otolaryngology, University of Pittsburgh School of Medicine

关键词: Exosomes;    Extracellular vesicles;    Adenosine;    Adenosine receptors;   

DOI  :  10.1007/s11302-020-09700-7

学科分类：分子生物学，细胞生物学和基因

来源: Springer

【 摘 要 】

Exosomes, small-sized extracellular vesicles, carry components of the purinergic pathway. The production by cells of exosomes carrying this pathway remains poorly understood. Here, we asked whether type 1, 2A, or 2B adenosine receptors (A1Rs, A2ARs, and A2BRs, respectively) expressed by producer cells are involved in regulating exosome production. Preglomerular vascular smooth muscle cells (PGVSMCs) were isolated from wildtype, A1R−/−, A2AR−/−, and A2BR−/− rats, and exosome production was quantified under normal or metabolic stress conditions. Exosome production was also measured in various cancer cells treated with pharmacologic agonists/antagonists of A1Rs, A2ARs, and A2BRs in the presence or absence of metabolic stress or cisplatin. Functional activity of exosomes was determined in Jurkat cell apoptosis assays. In PGVSMCs, A1R and A2AR constrained exosome production under normal conditions (p = 0.0297; p = 0.0409, respectively), and A1R, A2AR, and A2BR constrained exosome production under metabolic stress conditions. Exosome production from cancer cells was reduced (p = 0.0028) by the selective A2AR agonist CGS 21680. These exosomes induced higher levels of Jurkat apoptosis than exosomes from untreated cells or cells treated with A1R and A2BR agonists (p = 0.0474). The selective A2AR antagonist SCH 442416 stimulated exosome production under metabolic stress or cisplatin treatment, whereas the selective A2BR antagonist MRS 1754 reduced exosome production. Our findings indicate that A2ARs suppress exosome release in all cell types examined, whereas effects of A1Rs and A2BRs are dependent on cell type and conditions. Pharmacologic targeting of cancer with A2AR antagonists may inadvertently increase exosome production from tumor cells.

【 授权许可】

CC BY