Dataset Information

Proteomic profiling of rhabdomyosarcoma-derived exosomes yield functional role for extracellular vesicles

ABSTRACT: In this study, we interrogated the protein composition of exosomes purified from cell culture supernatants of 5 different RMS cell lines, by LC-MS/MS technology and analysis using bio-informatics tools. We attempted to characterize the differences and similarities between exosomes derived from ERMS and ARMS cells, and common as well as unique characteristics of RMS exosome protein content when compared to that of other cancer and non-cancer cells. Our results identify potential protein exosome biomarkers for RMS to be further investigated in future clinical studies.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Jingfu Zhao

LAB HEAD: Yehia S Mechref

PROVIDER: PXD007755 | Pride | 2019-08-29

REPOSITORIES: Pride

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Publications

Proteomic Profiling of Rhabdomyosarcoma-Derived Exosomes Yield Insights into Their Functional Role in Paracrine Signaling.

Rammal Ghina G Fahs Assil A Kobeissy Firas F Mechref Yehia Y Zhao Jingfu J Zhu Rui R Diab-Assaf Mona M Saab Raya R Ghayad Sandra E SE

Journal of proteome research 20190906 10

Exosomes are important intercellular communication vehicles, secreted into body fluids by multiple cell types, including tumor cells. They have been demonstrated to contribute to the metastatic progression of tumor cells through paracrine signaling. Tumor exosomes contain intact and functional proteins, mRNA and miRNA that may alter the cellular environment to favor tumor growth. We evaluated the protein cargo of exosomes derived from the childhood tumor rhabdomyosarcoma (RMS) and the molecular ...[more]

PMID: 31448612

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Project description:Rhabdomyosarcoma (RMS) is a highly malignant soft tissue sarcoma classified into two major histologic subtypes: embryonal (ERMS) and alveolar (ARMS). ARMS subtype is clinically more aggressive, and characterized by an oncogenic fusion protein PAX3-FOXO1 (P3F) that drives oncogenic cellular properties. To understand the role of the fusion oncoprotein in paracrine signaling, we focused on secreted exosomes, which have been demonstrated to contribute to metastasis in multiple tumor types. Mass spectrometry analysis of the protein cargo of exosomes isolated from C2C12 myoblasts transduced with P3F fusion gene revealed 52 deregulated proteins compared to control cells, with 26 enriched and 26 depleted proteins. Using both PANTHER gene classification and IPA software, we found that the main biological processes in which the 52 deregulated proteins are involved include “Catalytic activity”, “Binding”, “Metabolic process” and “Cellular process”. The pathways engaging the 26 enriched proteins include “14-3-3 mediated signaling”, “Cell cycle” and “ERK5, VEGF, IGF1and p70S6K signaling”. Main nodes in which deregulated exosome protein and miRNA intersected revealed pathways conferring protection from stress and promoting plasticity. Physiologically, exosomes derived from P3F-C2C12 cells activated ERK, 4-EBP1 and MMP-2, factors known to increase cell proliferation and invasion. In addition, they increased angiogenesis as evidenced by studies on HUVEC cells, and promoted stemness of MEFs and C2C12 cells. Treating stromal cells with exosomes from P3F-C2C12 cells protected them against effects of hydrogen peroxide (H2O2) in vitro, noting that P3F-C2C12 cells produce less ROS and are more resistant to induced exogenous oxidative stress as compared to control cells. Our findings highlight the role of P3F fusion protein in modulating exosome cargo to confer a protective effect on recipient cells against oxidative stress and promote plasticity and survival, potentially contributing to the known aggressive phenotype of the fusion gene-positive subtype of ARMS.

Dataset Information

Proteomic profiling of rhabdomyosarcoma-derived exosomes yield functional role for extracellular vesicles

Publications

Proteomic Profiling of Rhabdomyosarcoma-Derived Exosomes Yield Insights into Their Functional Role in Paracrine Signaling.

Similar Datasets

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