Akt Regulates Extracellular Vesicle Secretion in Hypoxia-adapted Multiple Myeloma RPMI8226 Cells.

IF 1.6 4区医学 Q4 ONCOLOGY

Anticancer research Pub Date : 2025-04-01 DOI:10.21873/anticanres.17521

Yuki Toda, Sayaka Nakayama, Yuna Yamamoto, Asuka Fujimoto, Shigekuni Hosogi, Eishi Ashihara

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引用次数: 0

Abstract

Background/aim: Hypoxia, a characteristic of the tumor microenvironment, affects tumor cell behavior by altering the secretion pattern of extracellular vesicles (EVs). We investigated the regulatory mechanism and biological significance of EV secretion in multiple myeloma (MM) cells grown under hypoxic culture conditions.

Materials and methods: Human MM cell lines (RPMI8226 and AMO1) were exposed to long-term hypoxia to generate hypoxia-adapted (HA) cells. EVs released into the culture supernatant were quantified by enzyme-linked immunosorbent assay. The expression of proteins involved in hypoxia-induced signaling was analyzed by western blotting. EV secretion was inhibited using GW4869.

Results: Exposure to hypoxia altered the amount of EVs secreted and the phosphorylation levels of Akt and its target molecule AS160. Pharmacological inhibition of Akt phosphorylation suppressed the increase in EV secretion and phosphorylated AS160 expression in HA RPMI8226 cells. GW4869 induced apoptosis in HA RPMI8226 cells, but not in the parental cell line, in the presence or absence of the secretome including EVs. GW4869 altered the expression of proteins related to glycolysis (HK2) and autophagy (LC3).

Conclusion: Akt signaling modulates EV secretion to maintain homeostasis in RPMI8226 cells exposed to hypoxic conditions.

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来源期刊

Anticancer research 医学-肿瘤学

CiteScore

3.70

自引率

10.00%

发文量

566

审稿时长

2 months

期刊介绍： ANTICANCER RESEARCH is an independent international peer-reviewed journal devoted to the rapid publication of high quality original articles and reviews on all aspects of experimental and clinical oncology. Prompt evaluation of all submitted articles in confidence and rapid publication within 1-2 months of acceptance are guaranteed. ANTICANCER RESEARCH was established in 1981 and is published monthly (bimonthly until the end of 2008). Each annual volume contains twelve issues and index. Each issue may be divided into three parts (A: Reviews, B: Experimental studies, and C: Clinical and Epidemiological studies). Special issues, presenting the proceedings of meetings or groups of papers on topics of significant progress, will also be included in each volume. There is no limitation to the number of pages per issue.