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Proteomic Analysis of Neuroblastoma‐Derived Exosomes: New Insights into a Metastatic Signature
Author(s) -
Colletti Marta,
Petretto Andrea,
Galardi Angela,
Di Paolo Virginia,
Tomao Luigi,
Lavarello Chiara,
Inglese Elvira,
Bruschi Maurizio,
Lopez Ana Amor,
Pascucci Luisa,
Geoerger Birgit,
Peinado Hector,
Locatelli Franco,
Di Giannatale Angela
Publication year - 2017
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.201600430
Subject(s) - microvesicles , neuroblastoma , metastasis , bone marrow , cancer research , primary tumor , biology , proteomics , tumor progression , tumor microenvironment , pathology , cancer , medicine , immunology , cell culture , microrna , tumor cells , biochemistry , genetics , gene
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.