Large oncosomes contain distinct protein cargo and represent a separate functional class of tumor-derived extracellular vesicles

被引：307

作者：

Minciacchi, Valentina R. ^{[1
,2
,3
]}

You, Sungyong ^{[1
,2
,3
]}

Spinelli, Cristiana ^{[1
,2
,3
]}

Morley, Samantha ^{[4
,5
]}

Zandian, Mandana ^{[1
,2
,3
]}

Aspuria, Paul-Joseph ^{[6
]}

Cavallini, Lorenzo ^{[1
,2
,3
,7
]}

Ciardiello, Chiara ^{[1
,2
,3
,8
]}

Sobreiro, Mariana Reis ^{[1
,2
,3
]}

Morello, Matteo ^{[1
,2
,3
]}

Kharmate, Geetanjali ^{[9
]}

Jang, Su Chul ^{[10
]}

Kim, Dae-Kyum ^{[10
]}

Hosseini-Beheshti, Elham ^{[9
]}

Guns, Emma Tomlinson ^{[9
]}

Gleave, Martin ^{[9
]}

Gho, Yong Song ^{[10
]}

Mathivanan, Suresh ^{[11
]}

Yang, Wei ^{[1
,2
,3
]}

Freeman, Michael R. ^{[1
,2
,3
,4
,5
]}

Di Vizio, Dolores ^{[1
,2
,3
,4
,5
]}

机构：

[1] Cedars Sinai Med Ctr, Dept Surg, Div Canc Biol & Therapeut, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA

[2] Cedars Sinai Med Ctr, Dept Biomed Sci, Div Canc Biol & Therapeut, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA

[3] Cedars Sinai Med Ctr, Dept Pathol & Lab Med, Div Canc Biol & Therapeut, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA

[4] Boston Childrens Hosp, Urol Dis Res Ctr, Boston, MA USA

[5] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA

[6] Cedars Sinai Med Ctr, Womens Canc Program, Los Angeles, CA 90048 USA

[7] Univ Florence, Dept Expt & Clin Biomed Sci, Florence, Italy

[8] IRCCS Ist Nazl Tumori G Pascale, Dept Res, Expt Pharmacol Unit, Naples, Italy

[9] Univ British Columbia, Vancouver Prostate Ctr, Dept Urol Sci, Vancouver, BC V5Z 1M9, Canada

[10] Pohang Univ Sci & Technol, Dept Life Sci, Pohang, South Korea

[11] La Trobe Univ, Dept Biochem, La Trobe Inst Mol Sci, Bundoora, Vic 3083, Australia

来源：

ONCOTARGET | 2015年 / 6卷 / 13期

基金：

美国国家卫生研究院; 新加坡国家研究基金会;

关键词：

Extracellular Vesicles; SILAC Proteomics; Cancer metabolism; Tumor progression; Amoeboid blebbing; HUMAN PROSTATE-CANCER; INTERCELLULAR TRANSFER; PROTEOMIC ANALYSIS; BONE-MARROW; EXOSOMES; CELLS; MICROVESICLES; PHENOTYPE; BIOMARKER; EXPRESSION;

D O I：

10.18632/oncotarget.3598

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Large oncosomes (LO) are atypically large (1-10 mu m diameter) cancer-derived extracellular vesicles (EVs), originating from the shedding of membrane blebs and associated with advanced disease. We report that 25% of the proteins, identified by a quantitative proteomics analysis, are differentially represented in large and nano-sized EVs from prostate cancer cells. Proteins enriched in large EVs included enzymes involved in glucose, glutamine and amino acid metabolism, all metabolic processes relevant to cancer. Glutamine metabolism was altered in cancer cells exposed to large EVs, an effect that was not observed upon treatment with exosomes. Large EVs exhibited discrete buoyant densities in iodixanol (OptiPrep (TM)) gradients. Fluorescent microscopy of large EVs revealed an appearance consistent with LO morphology, indicating that these structures can be categorized as LO. Among the proteins enriched in LO, cytokeratin 18 (CK18) was one of the most abundant (within the top 5th percentile) and was used to develop an assay to detect LO in the circulation and tissues of mice and patients with prostate cancer. These observations indicate that LO represent a discrete EV type that may play a distinct role in tumor progression and that may be a source of cancer-specific markers.

引用

页码：11327 / 11341

页数：15

共 61 条

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