Melanoma-Derived Exosomes Induce PD-1 Overexpression and Tumor Progression via Mesenchymal Stem Cell Oncogenic Reprogramming
oleh: 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
| Format: | Article |
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| Diterbitkan: | Frontiers Media S.A. 2019-10-01 |
Deskripsi
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.