Small extracellular vesicles convey the stress-induced adaptive responses of melanoma cells

• Published in: Scientific reports Vol. 9; no. 1; pp. 15329 - 19
• Main Authors: Harmati, Maria, Gyukity-Sebestyen, Edina, Dobra, Gabriella, Janovak, Laszlo, Dekany, Imre, Saydam, Okay, Hunyadi-Gulyas, Eva, Nagy, Istvan, Farkas, Attila, Pankotai, Tibor, Ujfaludi, Zsuzsanna, Horvath, Peter, Piccinini, Filippo, Kovacs, Maria, Biro, Tamas, Buzas, Krisztina
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 25.10.2019; Nature Publishing Group
• Subjects: 13/1; 13/100; 13/106; 13/31; 13/51; 14/19; 14/28; 14/3; 14/35; 14/63; 631/67; 631/80; 82; Animals; Bioinformatics; Cell adhesion & migration; Cell Cycle - drug effects; Cell interactions; Cell migration; Cell Movement - drug effects; Cell Proliferation - drug effects; Cell signaling; Cellular stress response; Communication; Doxorubicin - pharmacology; Endothelial Cells - drug effects; Endothelial Cells - pathology; Exosomes; Extracellular Matrix - drug effects; Extracellular Matrix - metabolism; Extracellular vesicles; Extracellular Vesicles - drug effects; Extracellular Vesicles - metabolism; Extracellular Vesicles - ultrastructure; Humanities and Social Sciences; Male; Melanoma; Melanoma, Experimental - pathology; Melanoma, Experimental - ultrastructure; Mesenchymal Stem Cells - cytology; Mesenchymal Stem Cells - drug effects; Mesenchymal Stem Cells - metabolism; Mesenchyme; Metal Nanoparticles - chemistry; Metal Nanoparticles - ultrastructure; Mice, Inbred C57BL; MicroRNAs - genetics; MicroRNAs - metabolism; multidisciplinary; Oxidative stress; Proteome - metabolism; Proteomes; Science; Science (multidisciplinary); Silver - chemistry; Stem cells; Stress, Physiological - drug effects; Titanium - chemistry; Tumor Microenvironment - drug effects; Tumors
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-51778-6

Exosomes are small extracellular vesicles (sEVs), playing a crucial role in the intercellular communication in physiological as well as pathological processes. Here, we aimed to study whether the melanoma-derived sEV-mediated communication could adapt to microenvironmental stresses. We compared B16F1 cell-derived sEVs released under normal and stress conditions, including cytostatic, heat and oxidative stress. The miRNome and proteome showed substantial differences across the sEV groups and bioinformatics analysis of the obtained data by the Ingenuity Pathway Analysis also revealed significant functional differences. The in silico predicted functional alterations of sEVs were validated by in vitro assays. For instance, melanoma-derived sEVs elicited by oxidative stress increased Ki-67 expression of mesenchymal stem cells (MSCs); cytostatic stress-resulted sEVs facilitated melanoma cell migration; all sEV groups supported microtissue generation of MSC-B16F1 co-cultures in a 3D tumour matrix model. Based on this study, we concluded that (i) molecular patterns of tumour-derived sEVs, dictated by the microenvironmental conditions, resulted in specific response patterns in the recipient cells; (ii) in silico analyses could be useful tools to predict different stress responses; (iii) alteration of the sEV-mediated communication of tumour cells might be a therapy-induced host response, with a potential influence on treatment efficacy.