期刊
THERANOSTICS
卷 12, 期 2, 页码 859-874出版社
IVYSPRING INT PUBL
DOI: 10.7150/thno.66274
关键词
nutrient deprivation; extracellular ATP; microparticles; tumor microenvironment; P2X7
资金
- Italian Association for Cancer Research [IG 13025, IG 18581]
- Ministry of Health of Italy [RF-2011-02348435]
- Ministry of Education of Italy (PRIN) [20178YTNWC]
- University of Ferrara
- European H2020 office through the COST Action [BM1406]
- AIRC [IG-23670]
- Telethon [GGP11139B]
- Ministry of University and Research of Italy, PRIN 2017 grant [E5L5P3]
- Italian Association for Cancer Research (AIRC) [IG16812, IG22837]
Nutrient deprivation promotes the release of extracellular ATP and leads to the accumulation of ATP-laden microparticles and naked mitochondria in the tumor microenvironment.
Rationale: Caloric restriction improves the efficacy of anti-cancer therapy. This effect is largely dependent on the increase of the extracellular ATP concentration in the tumor microenvironment (TME). Pathways for ATP release triggered by nutrient deprivation are largely unknown. Methods: The extracellular ATP (eATP) concentration was in vivo measured in the tumor microenvironment of Bl6F10-inoculated C57BI/6 mice with the pmeLuc probe. Alternatively, the pmeLuc-TG-mouse was used. Caloric restriction was in vivo induced with hydroxycitrate (HC). B16F10 melanoma cells or CT26 colon carcinoma cells were in vitro exposed to serum starvation to mimic nutrient deprivation. Energy metabolism was monitored by Seahorse. Microparticle release was measured by ultracentrifugation and by Nanosight. Results: Nutrient deprivation increases eATP release despite the dramatic inhibition of intracellular energy synthesis. Under these conditions oxidative phosphorylation was dramatically impaired, mitochondria fragmented and glycolysis and lactic acid release were enhanced. Nutrient deprivation stimulated a P2X7-dependent release of ATP-loaded, mitochondria-containing, microparticles as well as of naked mitochondria. Conclusions: Nutrient deprivation promotes a striking accumulation of eATP paralleled by a large release of ATP-laden microparticles and of naked mitochondria. This is likely to be a main mechanism driving the accumulation of eATP into the TME.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据