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Series GSE128681 Query DataSets for GSE128681
Status Public on Mar 22, 2019
Title Exosomes from CD99-deprived Ewing sarcoma cells reverse tumor malignancy by inhibiting cell migration and promoting neural differentiation
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Ewing sarcoma (EWS) is an aggressive mesenchymal tumor with unmet clinical need and significant social impacts on children, adolescents and young adults. CD99, a hallmark surface molecule of EWS, participates in crucial biological processes including cell migration, differentiation and death. EWS cells can release CD99 through exosomes, specialized extracellular vesicles with major cell communication roles. Here we show that, as a consequence of CD99 silencing, EWS cells deliver exosomes with oncosuppressive functions which significantly reduce tumor aggressiveness. These CD99-lacking microvesicles modulate gene expression of the EWS recipient cells, reduce proliferation and migration, in turn inducing a more differentiated less malignant phenotype. The most relevant effects were detected on the AP-1 signaling pathway whose regulation was found to be dependent on the specific cargo loaded in vesicles after CD99 shutdown. Investigation of the miRNA content of CD99-deprived exosomes identified miR-199a-3p as a key driver to reverse EWS malignancy in experimental models as well as in clinical specimens. All together our data provide evidence that the abrogation of CD99 in EWS tumor cells leads to produce and release exosomes capable to transfer their antineoplastic effects into the nearby tumor cells, suggesting a novel atypical role for these microvesicles in reversion of malignancy rather than in priming the soil for progression and metastatic seeding. This conceptually innovative approach might offer a new therapeutic opportunity to treat a tumor still refractory to most treatments.
 
Overall design The analysis was performed comparing the parental EWS cell line TC-71 and TC-71 after treatment with exosomes isolated by CD99-silenced cells. The aim of the study was to identify specific players responsible for the biological effects observed after exosome exposure.
 
Contributor(s) Astolfi A, Scotlandi K
Citation(s) 31209202
Submission date Mar 21, 2019
Last update date Jun 21, 2019
Contact name Annalisa Astolfi
E-mail(s) annalisa.astolfi@unibo.it
Phone +39 051 2144633
Organization name University of Bologna
Department "Giorgio Prodi" Cancer Research center
Lab Pediatric Oncology and Hematology lab
Street address via massarenti 11
City Bologna
ZIP/Postal code 40138
Country Italy
 
Platforms (1)
GPL17585 [HTA-2_0] Affymetrix Human Transcriptome Array 2.0 [probe set (exon) version]
Samples (4)
GSM3682445 TC71 biological replicate A
GSM3682446 TC71 biological replicate B
GSM3682447 TC71+exoTCsiCD99 biological replicate C
Relations
BioProject PRJNA528485

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Supplementary file Size Download File type/resource
GSE128681_RAW.tar 98.5 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table

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