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

Sebestyén, Edina and Harmati, Mária and Dobra, Gabriella and Németh, István B. and Mihály, Johanna and Zvara, Ágnes and Hunyadi-Gulyás, Éva Csilla and Katona, Róbert László and Nagy, István and Horváth, Péter and Bálind, Árpád and Szkalisity, Ábel and Pankotai, Tibor and Borsos, Barbara Nikolett and Szegletes, Zsolt and Buzás, Krisztina (2019) Melanoma-Derived Exosomes Induce PD-1 Overexpression and Tumor Progression via Mesenchymal Stem Cell Oncogenic Reprogramming. FRONTIERS IN IMMUNOLOGY, 10. ISSN 1664-3224

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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.

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