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

Maria Harmati, Edina Gyukity-Sebestyen, Gabriella Dobra, Laszlo Janovak, Imre Dekany, Okay Saydam, Eva Hunyadi-Gulyas, Istvan Nagy, Attila Farkas, Tibor Pankotai, Zsuzsanna Ujfaludi, Peter Horvath, Filippo Piccinini, Maria Kovacs, Tamas Biro, Krisztina Buzas

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Article number15329
JournalScientific Reports
Volume9
Issue number1
DOIs
Publication statusPublished - Dec 1 2019

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Small extracellular vesicles convey the stress-induced adaptive responses of melanoma cells'. Together they form a unique fingerprint.

  • Cite this

    Harmati, M., Gyukity-Sebestyen, E., Dobra, G., Janovak, L., Dekany, I., Saydam, O., Hunyadi-Gulyas, E., Nagy, I., Farkas, A., Pankotai, T., Ujfaludi, Z., Horvath, P., Piccinini, F., Kovacs, M., Biro, T., & Buzas, K. (2019). Small extracellular vesicles convey the stress-induced adaptive responses of melanoma cells. Scientific Reports, 9(1), [15329]. https://doi.org/10.1038/s41598-019-51778-6