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: Contribution to journalArticle

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 - Oct 18 2019

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Exosomes
Mesenchymal Stromal Cells
Melanoma
Programmed Cell Death 1 Receptor
Neoplasms
MicroRNAs
Population
Cellular Reprogramming
Proteins

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Melanoma-Derived Exosomes Induce PD-1 Overexpression and Tumor Progression via Mesenchymal Stem Cell Oncogenic Reprogramming. / Gyukity-Sebestyén, Edina; Harmati, Mária; Dobra, Gabriella; Németh, István B.; Mihály, Johanna; Zvara, Ágnes; Hunyadi-Gulyás, Éva; Katona, Róbert; Nagy, István; Horváth, Péter; Bálind, Árpád; Szkalisity, Ábel; Kovács, Mária; Pankotai, Tibor; Borsos, Barbara; Erdélyi, Miklós; Szegletes, Zsolt; Veréb, Zoltán J.; Buzás, Edit I.; Kemény, Lajos; Bíró, Tamás; Buzás, Krisztina.

In: Frontiers in immunology, Vol. 10, 2459, 18.10.2019.

Research output: Contribution to journalArticle

Gyukity-Sebestyén, E, Harmati, M, Dobra, G, Németh, IB, 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, ZJ, Buzás, EI, Kemény, L, Bíró, T & Buzás, K 2019, 'Melanoma-Derived Exosomes Induce PD-1 Overexpression and Tumor Progression via Mesenchymal Stem Cell Oncogenic Reprogramming', Frontiers in immunology, vol. 10, 2459. https://doi.org/10.3389/fimmu.2019.02459
Gyukity-Sebestyén, Edina ; Harmati, Mária ; Dobra, Gabriella ; Németh, István B. ; Mihály, Johanna ; Zvara, Ágnes ; Hunyadi-Gulyás, Éva ; Katona, Róbert ; Nagy, István ; Horváth, Péter ; Bálind, Árpád ; Szkalisity, Ábel ; Kovács, Mária ; Pankotai, Tibor ; Borsos, Barbara ; Erdélyi, Miklós ; Szegletes, Zsolt ; Veréb, Zoltán J. ; Buzás, Edit I. ; Kemény, Lajos ; Bíró, Tamás ; Buzás, Krisztina. / Melanoma-Derived Exosomes Induce PD-1 Overexpression and Tumor Progression via Mesenchymal Stem Cell Oncogenic Reprogramming. In: Frontiers in immunology. 2019 ; Vol. 10.
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AU - Németh, István B.

AU - Mihály, Johanna

AU - Zvara, Ágnes

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AU - Erdélyi, Miklós

AU - Szegletes, Zsolt

AU - Veréb, Zoltán J.

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