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

• Published in: Frontiers in immunology Vol. 10; p. 2459
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 18-10-2019
• Subjects: exosome; Immunology; melanoma/tumor progression; PD-1; reprogramming; signalization pattern; stem cell; reprogramming; stem cell; metastasis; melanoma/tumor progression; signalization pattern; PD-1; exosome
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2019.02459

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 (mMSC
) from naïve mesenchymal stem cells (MSCs). Exosomes and mMSC
cells induce tumor progression and expression of oncogenic factors
. 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.