Doxorubicin Expands in Vivo Secretion of Circulating Exosome in Mice

Modulation of tumor immunity is a known factor in the antitumor activity of many chemotherapeutic agents. Exosomes are extracellular nanometric vesicles that are released by almost all types of cells, which includes cancer cells. These vesicles play a crucial role in tumor immunity. Many in vitro st...

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Bibliographic Details
Published in:Biological & pharmaceutical bulletin 2018/07/01, Vol.41(7), pp.1078-1083
Main Authors: Emam, Sherif E., Ando, Hidenori, Lila, Amr Selim Abu, Kobayashi, Shinya, Shimizu, Taro, Okuhira, Keiichiro, Ishima, Yu, Ishida, Tatsuhiro
Format: Article
Language:English
Subjects:
Antineoplastic drugs
Antitumor activity
Antitumor agents
Cancer
CD63 antigen
CD9 antigen
chemotherapeutic agent
Chemotherapy
Doxorubicin
exosome
Exosomes
Immunosuppressive agents
Injection
Intravenous administration
liposomal doxorubicin
Mice
Secretions
Size distribution
Spleen
Splenectomy
Vesicles
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Summary:Modulation of tumor immunity is a known factor in the antitumor activity of many chemotherapeutic agents. Exosomes are extracellular nanometric vesicles that are released by almost all types of cells, which includes cancer cells. These vesicles play a crucial role in tumor immunity. Many in vitro studies have reproduced the aggressive secretion of exosomes following treatment with conventional anticancer drugs. Nevertheless, how chemotherapeutic agents including nanomedicines such as Doxil® affect the in vivo secretion of exosomes is yet to be elucidated. In this study, the effect of intravenous injection of either free doxorubicin (DXR) or liposomal DXR formulation (Doxil®) on exosome secretion was evaluated in BALB/c mice. Exosomes were isolated from serum by using an ExoQuick™ kit. Free DXR treatment markedly increased serum exosome levels in a post-injection time-dependent manner, while Doxil® treatment did not. Exosomal size distribution and marker protein expressions (CD9, CD63, and TSG101) were studied. The physical/biological characteristics of treatment-induced exosomes were comparable to those of control mice. Interestingly, splenectomy significantly suppressed the copious exosomal secretions induced by free DXR. Collectively, our results indicate that conventional anticancer agents induce the secretion of circulating exosomes, presumably via stimulating immune cells of the spleen. As far as we know, this study represents the first report indicating that conventional chemotherapeutics may induce exosome secretion which might, in turn, contribute partly to the antitumor effect of chemotherapeutic agents.
ISSN:0918-6158
1347-5215
DOI:10.1248/bpb.b18-00202