Exosomes enriched in stemness/metastatic-related mRNAS promote oncogenic potential in breast cancer

富含干细胞/转移相关 mRNA 的外泌体增强乳腺癌的致癌潜力

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作者:Marta Rodríguez, Javier Silva, Alberto Herrera, Mercedes Herrera, Cristina Peña, Paloma Martín, Beatriz Gil-Calderón, María Jesús Larriba, M Josés Coronado, Beatriz Soldevilla, Víctor S Turrión, Mariano Provencio, Antonio Sánchez, Félix Bonilla, Vanesa García-Barberán

Abstract

Cancer cells efficiently transfer exosome contents (essentially mRNAs and microRNAs) to other cell types, modifying immune responses, cell growth, angiogenesis and metastasis. Here we analyzed the exosomes release by breast tumor cells with different capacities of stemness/metastasis based on CXCR4 expression, and evaluated their capacity to generate oncogenic features in recipient cells. Breast cancer cells overexpressing CXCR4 showed an increase in stemness-related markers, and in proliferation, migration and invasion capacities. Furthermore, recipient cells treated with exosomes from CXCR4-cells showed increased in the same abilities. Moreover, inoculation of CXCR4-cell-derived exosomes in immunocompromised mice stimulated primary tumor growth and metastatic potential. Comparison of nucleic acids contained into exosomes isolated from patients revealed a "stemness and metastatic" signature in exosomes of patients with worse prognosis. Finally, our data supported the view that cancer cells with stem-like properties show concomitant metastatic behavior, and their exosomes stimulate tumor progression and metastasis. Exosomes-derived nucleic acids from plasma of breast cancer patients are suitable markers in the prognosis of such patients.

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