Large and small extracellular vesicles released by glioma cells in vitro and in vivo

被引：64

作者：

Yekula, Anudeep ^{[1
]}

Minciacchi, Valentina R. ^{[2
]}

Morello, Matteo ^{[2
]}

Shao, Huilin ^{[3
]}

Park, Yongil ^{[3
]}

Zhang, Xuan ^{[4
,5
,6
]}

Muralidharan, Koushik ^{[1
]}

Freeman, Michael R. ^{[2
,7
]}

Weissleder, Ralph ^{[3
,8
]}

Lee, Hakho ^{[3
]}

Carter, Bob ^{[1
]}

Breakefield, Xandra O. ^{[4
,5
,6
]}

Di Vizio, Dolores ^{[2
,7
]}

Balaj, Leonora ^{[1
]}

机构：

[1] Massachusetts Gen Hosp, Dept Neurosurg, 185 Cambridge St, Boston, MA 02114 USA

[2] Cedars Sinai Med Ctr, Dept Surg Pathol & Lab Med, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA

[3] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA

[4] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA

[5] Massachusetts Gen Hosp, Program Neurosci, Boston, MA 02114 USA

[6] Harvard Med Sch, Boston, MA 02115 USA

[7] Harvard Med Sch, Boston Childrens Hosp, Urol Dis Res Ctr, Boston, MA 02115 USA

[8] Harvard Med Sch, Dept Syst Biol, Boston, MA 02115 USA

来源：

JOURNAL OF EXTRACELLULAR VESICLES | 2020年 / 9卷 / 01期

基金：

美国国家卫生研究院;

关键词：

Extracellular vesicles; large extracellular vesicles; small extracellular vesicles; biomarkers; glioma; LARGE ONCOSOMES; INTERCELLULAR TRANSFER; LIQUID BIOPSY; TUMOR; EGFRVIII; GROWTH;

D O I：

10.1080/20013078.2019.1689784

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Tumour cells release diverse populations of extracellular vesicles (EVs) ranging in size, molecular cargo, and function. We sought to characterize mRNA and protein content of EV subpopulations released by human glioblastoma (GBM) cells expressing a mutant form of epidermal growth factor receptor (U87(EGFRvIII)) in vitro and in vivo with respect to size, morphology and the presence of tumour cargo. The two EV subpopulations purified from GBM U87(EGFRvIII) cancer cells, non-cancer human umbilical vein endothelial cells (HUVEC; control) and serum of U87(EGFRvIII) glioma-bearing mice using differential centrifugation (EVs that sediment at 10,000 x g or 100,000 x g are termed large EVs and small EVs, respectively) were characterized using transmission electron microscopy (TEM), confocal microscopy, nanoparticle tracking analysis (NTA), flow cytometry, immunofluorescence (IF), quantitative-polymerase chain reaction (qPCR), droplet digital polymerase chain reaction (ddPCR) and micro-nuclear magnetic resonance (mu NMR). We report that both U87(EGFRvIII) and HUVEC release a similar number of small EVs, but U87(EGFRvIII) glioma cells alone release a higher number of large EVs compared to non-cancer HUVEC. The EGFRvIII mRNA from the two EV subpopulations from U87(EGFRvIII) glioma cells was comparable, while the EGFR protein (wild type + vIII) levels are significantly higher in large EVs. Similarly, EGFRvIII mRNA in large and small EVs isolated from the serum of U87(EGFRvIII) glioma-bearing mice is comparable, while the EGFR protein (wild type + vIII) levels are significantly higher in large EVs. Here we report for the first time a direct comparison of large and small EVs released by glioma U87(EGFRvIII) cells and from serum of U87(EGFRvIII) glioma-bearing mice. Both large and small EVs contain tumour-specific EGFRvIII mRNA and proteins and combining these platforms may be beneficial in detecting rare mutant events in circulating biofluids.

引用

页数：10

共 42 条

[41] Multicore Assemblies Potentiate Magnetic Properties of Biomagnetic Nanoparticles
Yoon, Tae-Jong
Lee, Hakho
Shao, Huilin
Hilderbrand, Scott A.
Weissleder, Ralph
[J]. ADVANCED MATERIALS, 2011, 23 (41) : 4793 - +
[42] Blood-based biomarkers for the diagnosis and monitoring of gliomas
Zachariah, Marcus A.
Oliveira-Costa, Joao Paulo
Carter, Bob S.
Stott, Shannon L.
Nahed, Brian V.
[J]. NEURO-ONCOLOGY, 2018, 20 (09) : 1155 - 1161

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