Journal
FRONTIERS IN IMMUNOLOGY
Volume 10, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2019.02459
Keywords
PD-1; exosome; melanoma; tumor progression; stem cell; reprogramming; signalization pattern; metastasis
Categories
Funding
- National Research, Development and Innovation Fund of Hungary under the NKFI-6-K funding scheme [11493, GINOP-2.3.2-15-2016-00015, GINOP-2.2.1-152017-00052]
- Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences [UNKP-19-4]
- University of Szeged
- Hungarian Brain Research Program [KTIA_13_NAP-A-I/14]
- [GINOP-2.3.2-15-2016-00036]
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Recently, it has been described that programmed cell death protein 1 (PD-1) overexpressing melanoma cells are highly aggressive. However, until now it has not been defined which factors lead to the generation of PD-1 overexpressing subpopulations. Here, we present that melanoma-derived exosomes, conveying oncogenic molecular reprogramming, induce the formation of a melanoma-like, PD-1 overexpressing cell population (mMSC(PD-1+)) from naive mesenchymal stem cells (MSCs). Exosomes and mMSC(PD-1+) cells induce tumor progression and expression of oncogenic factors in vivo. Finally, we revealed a characteristic, tumorigenic signaling network combining the upregulated molecules (e.g., PD-1, MET, RAF1, BCL2, MTOR) and their upstream exosomal regulating proteins and miRNAs. Our study highlights the complexity of exosomal communication during tumor progression and contributes to the detailed understanding of metastatic processes.
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