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Proteomic Analysis of Neuroblastoma‐Derived Exosomes: New Insights into a Metastatic Signature

微泡 神经母细胞瘤 转移 骨髓 癌症研究 原发性肿瘤 生物 蛋白质组学 肿瘤进展 肿瘤微环境 病理 癌症 医学 免疫学 细胞培养 小RNA 肿瘤细胞 基因 生物化学 遗传学
作者
Marta Colletti,Andrea Petretto,Angela Galardi,Virginia Di Paolo,Luigi Tomao,Chiara Lavarello,Elvira Inglese,Maurizio Bruschi,Ana Amor López,Luisa Pascucci,Birgit Geoerger,Héctor Peinado,Franco Locatelli,Angela Di Giannatale
出处
期刊:Proteomics [Wiley]
卷期号:17 (23-24) 被引量:40
标识
DOI:10.1002/pmic.201600430
摘要

Neuroblastoma (NB) is the most common extracranial pediatric solid tumor. Around 70% of patients with metastatic disease at diagnosis present bone-marrow infiltration, which is considered a marker of poor outcome; however, the mechanism underlying this specific tropism has to be elucidated. Tumor-derived exosomes may support metastatic progression in several tumors by interacting with the microenvironment, and may serve as tumor biomarkers. The main objective of this study is to identify an exosomal signature associated with NB metastatic bone-marrow dissemination. Therefore, the proteomic cargo of exosomes isolated from NB cell lines derived from primary tumor and bone-marrow metastasis is characterized. The comparison among exosomal proteins show 15 proteins exclusively present in primary tumor-derived exosomes, mainly involved in neuronal development, and 6 proteins in metastasis-derived exosomes related to cancer progression. Significant proteins obtain with statistical analysis performed between the two groups, reveal that primary tumor exosomes contain a higher level of proteins involved in extra-cellular matrix (ECM) assembly and adhesion, as well as in neuronal development. Exosomes isolated from bone-marrow metastasis exhibit proteins involved in ameboidal cell migration and mitochondrial activity. This work suggests that proteomic profiling of NB-derived exosomes reflects the tumor stage and may be considered as potential tumor biomarker.
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