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

Edina Gyukity-Sebestyén, Mária Harmati, Gabriella Dobra, István B. Németh, Johanna Mihály, Ágnes Zvara, Éva Hunyadi-Gulyás, Róbert Katona, István Nagy, Péter Horváth, Árpád Bálind, Ábel Szkalisity, Mária Kovács, Tibor Pankotai, Barbara Borsos, Miklós Erdélyi, Zsolt Szegletes, Zoltán J. Veréb, Edit I. Buzás, Lajos KeményTamás Bíró, Krisztina Buzás

Research output: Article

4 Citations (Scopus)

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.

Original languageEnglish
Article number2459
JournalFrontiers in immunology
Volume10
DOIs
Publication statusPublished - okt. 18 2019

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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  • Cite this

    Gyukity-Sebestyén, E., Harmati, M., Dobra, G., Németh, I. B., Mihály, J., Zvara, Á., Hunyadi-Gulyás, É., Katona, R., Nagy, I., Horváth, P., Bálind, Á., Szkalisity, Á., Kovács, M., Pankotai, T., Borsos, B., Erdélyi, M., Szegletes, Z., Veréb, Z. J., Buzás, E. I., ... Buzás, K. (2019). Melanoma-Derived Exosomes Induce PD-1 Overexpression and Tumor Progression via Mesenchymal Stem Cell Oncogenic Reprogramming. Frontiers in immunology, 10, [2459]. https://doi.org/10.3389/fimmu.2019.02459