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Front Immunol. 2019 Oct 18;10:2459. doi: 10.3389/fimmu.2019.02459. eCollection 2019.

Melanoma-Derived Exosomes Induce PD-1 Overexpression and Tumor Progression via Mesenchymal Stem Cell Oncogenic Reprogramming.

Author information

1
Laboratory of Microscopic Image Analysis and Machine Learning, Institute of Biochemistry, Biological Research Centre of Hungarian Academy of Sciences, Szeged, Hungary.
2
Doctoral School of Interdisciplinary Sciences, Faculty of Medicine, University of Szeged, Szeged, Hungary.
3
Department of Dermatology and Allergology, University of Szeged, Szeged, Hungary.
4
Department of Immunology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
5
Laboratory of Functional Genomics, Institute of Genetics, Biological Research Centre of Hungarian Academy of Sciences, Szeged, Hungary.
6
Laboratory of Proteomics Research, Institute of Biochemistry, Biological Research Centre of Hungarian Academy of Sciences, Szeged, Hungary.
7
Artificial Chromosome and Stem Cell Research Laboratory, Institute of Genetics, Biological Research Centre of Hungarian Academy of Sciences, Szeged, Hungary.
8
Sequencing Platform, Institute of Biochemistry, Biological Research Centre of Hungarian Academy of Sciences, Szeged, Hungary.
9
Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Szeged, Szeged, Hungary.
10
Department of Biochemistry and Molecular Biology, Faculty of Science and Informatics, University of Szeged, Szeged, Hungary.
11
Advanced Optical Imaging Group, Department of Optics and Quantum Electronics, Faculty of Science and Informatics, University of Szeged, Szeged, Hungary.
12
Atomic Force Microscope Laboratory, Institute of Biophysics, Biological Research Centre of Hungarian Academy of Sciences, Szeged, Hungary.
13
MTA-SE Immuno-proteogenomics Extracellular Vesicle Research Group, Department of Genetics, Cell- and Immunobiology, Faculty of Medicine, Semmelweis University, Budapest, Hungary.
14
Department of Oral Biology and Experimental Dental Research, Faculty of Dentistry, University of Szeged, Szeged, Hungary.

Abstract

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 (mMSCPD-1+) from naïve mesenchymal stem cells (MSCs). Exosomes and mMSCPD-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.

KEYWORDS:

PD-1; exosome; melanoma/tumor progression; metastasis; reprogramming; signalization pattern; stem cell

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