Circulating miRNAs in Small Extracellular Vesicles Secreted by a Human Melanoma Xenograft in Mouse Brains

被引:11
作者
Guglielmi, Loredana [1 ]
Nardella, Marta [2 ]
Musa, Carla [3 ]
Cifola, Ingrid [1 ]
Porru, Manuela [4 ]
Cardinali, Beatrice [3 ]
Iannetti, Ilaria [3 ]
Di Pietro, Chiara [3 ]
Bolasco, Giulia [5 ]
Palmieri, Valentina [6 ,7 ]
Vilardo, Laura [1 ]
Panini, Nicolo [8 ]
Bonaventura, Fabrizio [3 ]
Papi, Massimiliano [6 ,7 ]
Scavizzi, Ferdinando [3 ]
Raspa, Marcello [3 ]
Leonetti, Carlo [4 ]
Falcone, Germana [3 ]
Felsani, Armando [9 ]
D'Agnano, Igea [1 ]
机构
[1] CNR, Inst Biomed Technol ITB, I-20090 Segrate, Italy
[2] Bambino Gesu Pediat Hosp, Dept Neurosci, Unit Neuromuscular & Neurodegenerat Disorders, IRCCS, I-00146 Rome, Italy
[3] CNR, Inst Biochem & Cell Biol IBBC, I-00015 Monterotond, Italy
[4] UOSD SAFU IRCCS Regina Elena Canc Inst, I-00168 Rome, Italy
[5] EMBL Mouse Biol Unit, I-00015 Monterotondo, Italy
[6] Fdn Policlin Univ A Gemelli IRCSS, I-00168 Rome, Italy
[7] Univ Cattolica Sacro Cuore, Ist Fis, I-00168 Rome, Italy
[8] Ist Ric Farmacol Mario Negri IRCCS, Lab Canc Pharmacol, Dept Oncol, I-20156 Milan, Italy
[9] Genomnia Srl, I-20091 Bresso, Italy
关键词
melanoma; circulating miRNAs; small extracellular vesicles; INTERCELLULAR-COMMUNICATION; MALIGNANT-MELANOMA; TUMOR-GROWTH; CELL; MICRORNAS; CANCER; EXOSOMES; PROLIFERATION; INHIBITION; EXPRESSION;
D O I
10.3390/cancers12061635
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The identification of liquid biomarkers remains a major challenge to improve the diagnosis of melanoma patients with brain metastases. Circulating miRNAs packaged into tumor-secreted small extracellular vesicles (sEVs) contribute to tumor progression. To investigate the release of tumor-secreted miRNAs by brain metastasis, we developed a xenograft model where human metastatic melanoma cells were injected intracranially in nude mice. The comprehensive profiles of both free miRNAs and those packaged in sEVs secreted by the melanoma cells in the plasma demonstrated that most (80%) of the sEV-associated miRNAs were also present in serum EVs from a cohort of metastatic melanomas, included in a publicly available dataset. Remarkably, among them, we found three miRNAs (miR-224-5p, miR-130a-3p and miR-21-5p) in sEVs showing a trend of upregulation during melanoma progression. Our model is proven to be valuable for identifying miRNAs in EVs that are unequivocally secreted by melanoma cells in the brain and could be associated to disease progression.
引用
收藏
页码:1 / 22
页数:23
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