Dataset Information

Proteomic Profiling of Retinoblastoma-Derived Exosomes Reveals Potential Biomarkers of Vitreous Seeding.

ABSTRACT: Retinoblastoma (RB) is the most common tumor of the eye in early childhood. Although recent advances in conservative treatment have greatly improved the visual outcome, local tumor control remains difficult in the presence of massive vitreous seeding. Traditional biopsy has long been considered unsafe in RB, due to the risk of extraocular spread. Thus, the identification of new biomarkers is crucial to design safer diagnostic and more effective therapeutic approaches. Exosomes, membrane-derived nanovesicles that are secreted abundantly by aggressive tumor cells and that can be isolated from several biological fluids, represent an interesting alternative for the detection of tumor-associated biomarkers. In this study, we defined the protein signature of exosomes released by RB tumors (RBT) and vitreous seeding (RBVS) primary cell lines by high resolution mass spectrometry. A total of 5666 proteins were identified. Among these, 5223 and 3637 were expressed in exosomes RBT and one RBVS group, respectively. Gene enrichment analysis of exclusively and differentially expressed proteins and network analysis identified in RBVS exosomes upregulated proteins specifically related to invasion and metastasis, such as proteins involved in extracellular matrix (ECM) remodeling and interaction, resistance to anoikis and the metabolism/catabolism of glucose and amino acids.

SUBMITTER: Galardi A

PROVIDER: S-EPMC7352325 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Proteomic Profiling of Retinoblastoma-Derived Exosomes Reveals Potential Biomarkers of Vitreous Seeding.

Galardi Angela A Colletti Marta M Lavarello Chiara C Di Paolo Virginia V Mascio Paolo P Russo Ida I Cozza Raffaele R Romanzo Antonino A Valente Paola P De Vito Rita R Pascucci Luisa L Peinado Hector H Carcaboso Angel M AM Petretto Andrea A Locatelli Franco F Di Giannatale Angela A

Cancers 20200612 6

Retinoblastoma (RB) is the most common tumor of the eye in early childhood. Although recent advances in conservative treatment have greatly improved the visual outcome, local tumor control remains difficult in the presence of massive vitreous seeding. Traditional biopsy has long been considered unsafe in RB, due to the risk of extraocular spread. Thus, the identification of new biomarkers is crucial to design safer diagnostic and more effective therapeutic approaches. Exosomes, membrane-derived ...[more]

PMID: 32545553

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Project description:Developing tumors continuously release nano-sized vesicles that represent circulating "fingerprints" of the tumor's identity. In gastrointestinal stromal tumor (GIST), we have previously reported that these tumors release "oncosomes" carrying the constitutively activated tyrosine kinase (TK) receptor KIT. Despite the clinical utility of TK inhibitors, such as imatinib mesylate (IM), recurrence and metastasis are clinical problems that urge the need to identify new tumor-derived molecules. To this aim, we performed the first high quality proteomic study of GIST-derived exosomes (GDEs) and identified 1,060 proteins composing the core GDE proteome (cGDEp). The cGDEp was enriched in diagnostic markers (e.g. KIT, CD34, ANO1, PROM1, PRKCQ, and ENG), as well as proteins encoded by genes previously reported expressed in GIST (e.g. DPP4, FHL1, CDH11, and KCTD12). Many of these proteins were validated using cell lines, patient-derived KIT+ exosomes, and GIST tissues. We further show that in vitro and in vivo-derived GDE, carry proteins associated with IM response, such as Sprouty homolog 4 (SPRY4), surfeit 4 (SURF4), ALIX, and the cGMP-dependent 3',5'-cyclic phosphodiesterase 2A (PDE2A). Additionally, we report that the total exosome levels and exosome-associated KIT and SPRY4 protein levels have therapeutic values. In fact, molecular characterization of in vivo-derived KIT+ exosomes indicate significant sorting of p-KITTyr719, total KIT, and SPRY4 after IM-treatment of metastatic patients as compared with the pre-IM levels. Our data suggest that analysis of circulating exosomes levels and molecular markers of IM response in GIST patients with primary and metastatic disease is suitable to develop liquid based biopsies for the diagnosis, prognosis, and monitoring of response to treatment of these tumors. In summary, these findings provide the first insight into the proteome of GIST-derived oncosomes and offers a unique opportunity to further understand their oncogenic elements which contribute to tumorigenesis and drug resistance. Data are available via ProteomeXchange with identifier PXD007997.

Dataset Information

Proteomic Profiling of Retinoblastoma-Derived Exosomes Reveals Potential Biomarkers of Vitreous Seeding.

Publications

Proteomic Profiling of Retinoblastoma-Derived Exosomes Reveals Potential Biomarkers of Vitreous Seeding.

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