Exosomes derived from mesenchymal stem cells enhance radiotherapy-induced cell death in tumor and metastatic tumor foci
MetadataShow full item record
AuthorArujo Farias, Virgínea de; O'Valle Ravassa, Francisco Javier; Serrano Saenz, Santiago; Anderson, Per Olof; Andrés, Eduardo; López-Peñalver, Jesús; Tovar Galvez, Maria Isabel; Nieto, Ana; Santos, Ana; Martín, Francisco; Expósito, José; Oliver, Javier; Ruiz De Almodóvar Rivera, José Mariano
Experimental radiotherapyBystander effectAbscopal effectMesenchymal stem cellsCell therapyMetastasis spreadProteomic analysisAnnexin A1Melanoma xenograft
de Araujo Farias, V., O’Valle, F., Serrano-Saenz, S., Anderson, P., Andrés, E., López-Peñalver, J., ... & Expósito, J. (2018). Exosomes derived from mesenchymal stem cells enhance radiotherapy-induced cell death in tumor and metastatic tumor foci. Molecular cancer, 17(1), 122.
SponsorshipThis work was supported by CNPq, Conselho Nacional de Desenvolvimento Científico e Tecnológico – Brasil, Junta de Andalucía, project of Excellence from Junta de Andalucía P12-CTS-383 to FJO, Spanish Ministry of Economy and Competitiveness SAF2015-70520-R to FJO and JMRdA, RTICC RD12/0036/0026 and CIBER Cáncer ISCIII CB16/12/00421 to FJO.
We have recently shown that radiotherapy may not only be a successful local and regional treatment but, when combined with MSCs, may also be a novel systemic cancer therapy. This study aimed to investigate the role of exosomes derived from irradiated MSCs in the delay of tumor growth and metastasis after treatment with MSC + radiotherapy (RT). The tumor cell loss rates found after treatment with the combination of MSC and RT and for exclusive RT, were: 44.4% % and 12,1%, respectively. Concomitant and adjuvant use of RT and MSC, increased the mice surviving time 22,5% in this group, with regard to the group of mice treated with exclusive RT and in a 45,3% respect control group. Moreover, the number of metastatic foci found in the internal organs of the mice treated with MSC + RT was 60% less than the mice group treated with RT alone. We reasoned that the exosome secreted by the MSC, could be implicated in tumor growth delay and metastasis control after treatment. Our results show that exosomes derived form MSCs, combined with radiotherapy, are determinant in the enhancement of radiation effects observed in the control of metastatic spread of melanoma cells and suggest that exosome-derived factors could be involved in the bystander, and abscopal effects found after treatment of the tumors with RT plus MSC. Radiotherapy itself may not be systemic, although it might contribute to a systemic effect when used in combination with mesenchymal stem cells owing the ability of irradiated MSCs-derived exosomes to increase the control of tumor growth and metastasis.