Frontiers in Immunology (Oct 2019)
Melanoma-Derived Exosomes Induce PD-1 Overexpression and Tumor Progression via Mesenchymal Stem Cell Oncogenic Reprogramming
- Edina Gyukity-Sebestyén,
- Edina Gyukity-Sebestyén,
- Mária Harmati,
- Mária Harmati,
- Gabriella Dobra,
- Gabriella Dobra,
- István B. Németh,
- Johanna Mihály,
- Ágnes Zvara,
- Éva Hunyadi-Gulyás,
- Róbert Katona,
- István Nagy,
- Péter Horváth,
- Árpád Bálind,
- Ábel Szkalisity,
- Mária Kovács,
- Mária Kovács,
- Tibor Pankotai,
- Barbara Borsos,
- Miklós Erdélyi,
- Zsolt Szegletes,
- Zoltán J. Veréb,
- Edit I. Buzás,
- Lajos Kemény,
- Tamás Bíró,
- Krisztina Buzás,
- Krisztina Buzás
Affiliations
- Edina Gyukity-Sebestyén
- Laboratory of Microscopic Image Analysis and Machine Learning, Institute of Biochemistry, Biological Research Centre of Hungarian Academy of Sciences, Szeged, Hungary
- Edina Gyukity-Sebestyén
- Doctoral School of Interdisciplinary Sciences, Faculty of Medicine, University of Szeged, Szeged, Hungary
- Mária Harmati
- Laboratory of Microscopic Image Analysis and Machine Learning, Institute of Biochemistry, Biological Research Centre of Hungarian Academy of Sciences, Szeged, Hungary
- Mária Harmati
- Doctoral School of Interdisciplinary Sciences, Faculty of Medicine, University of Szeged, Szeged, Hungary
- Gabriella Dobra
- Laboratory of Microscopic Image Analysis and Machine Learning, Institute of Biochemistry, Biological Research Centre of Hungarian Academy of Sciences, Szeged, Hungary
- Gabriella Dobra
- Doctoral School of Interdisciplinary Sciences, Faculty of Medicine, University of Szeged, Szeged, Hungary
- István B. Németh
- Department of Dermatology and Allergology, University of Szeged, Szeged, Hungary
- Johanna Mihály
- Department of Immunology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
- Ágnes Zvara
- Laboratory of Functional Genomics, Institute of Genetics, Biological Research Centre of Hungarian Academy of Sciences, Szeged, Hungary
- Éva Hunyadi-Gulyás
- Laboratory of Proteomics Research, Institute of Biochemistry, Biological Research Centre of Hungarian Academy of Sciences, Szeged, Hungary
- Róbert Katona
- Artificial Chromosome and Stem Cell Research Laboratory, Institute of Genetics, Biological Research Centre of Hungarian Academy of Sciences, Szeged, Hungary
- István Nagy
- Sequencing Platform, Institute of Biochemistry, Biological Research Centre of Hungarian Academy of Sciences, Szeged, Hungary
- Péter Horváth
- Laboratory of Microscopic Image Analysis and Machine Learning, Institute of Biochemistry, Biological Research Centre of Hungarian Academy of Sciences, Szeged, Hungary
- Árpád Bálind
- Laboratory of Microscopic Image Analysis and Machine Learning, Institute of Biochemistry, Biological Research Centre of Hungarian Academy of Sciences, Szeged, Hungary
- Ábel Szkalisity
- Laboratory of Microscopic Image Analysis and Machine Learning, Institute of Biochemistry, Biological Research Centre of Hungarian Academy of Sciences, Szeged, Hungary
- Mária Kovács
- Laboratory of Microscopic Image Analysis and Machine Learning, Institute of Biochemistry, Biological Research Centre of Hungarian Academy of Sciences, Szeged, Hungary
- Mária Kovács
- Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Szeged, Szeged, Hungary
- Tibor Pankotai
- 0Department of Biochemistry and Molecular Biology, Faculty of Science and Informatics, University of Szeged, Szeged, Hungary
- Barbara Borsos
- 0Department of Biochemistry and Molecular Biology, Faculty of Science and Informatics, University of Szeged, Szeged, Hungary
- Miklós Erdélyi
- 1Advanced Optical Imaging Group, Department of Optics and Quantum Electronics, Faculty of Science and Informatics, University of Szeged, Szeged, Hungary
- Zsolt Szegletes
- 2Atomic Force Microscope Laboratory, Institute of Biophysics, Biological Research Centre of Hungarian Academy of Sciences, Szeged, Hungary
- Zoltán J. Veréb
- Department of Dermatology and Allergology, University of Szeged, Szeged, Hungary
- Edit I. Buzás
- 3MTA-SE Immuno-proteogenomics Extracellular Vesicle Research Group, Department of Genetics, Cell- and Immunobiology, Faculty of Medicine, Semmelweis University, Budapest, Hungary
- Lajos Kemény
- Department of Dermatology and Allergology, University of Szeged, Szeged, Hungary
- Tamás Bíró
- Department of Immunology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
- Krisztina Buzás
- Laboratory of Microscopic Image Analysis and Machine Learning, Institute of Biochemistry, Biological Research Centre of Hungarian Academy of Sciences, Szeged, Hungary
- Krisztina Buzás
- 4Department of Oral Biology and Experimental Dental Research, Faculty of Dentistry, University of Szeged, Szeged, Hungary
- DOI
- https://doi.org/10.3389/fimmu.2019.02459
- Journal volume & issue
-
Vol. 10
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
