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

Cancer cells efficiently transfer exosome contents (essentially mRNAs and microRNAs) to other cell types, modifying immune responses, cell growth, angiogenesis and metastasis. Here researchers from the IDIPHIM 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, this 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.

Metastasis after fat pad injection of MDA-MB-231^FLuc cells in mice treated with exosomes. A. Ex vivo D-luciferin-based F^Luc-BLI images of excised lung, brain, lymph nodes and spleen of a representative mouse. B. Quantification of total photon flux in lymph nodes (*p ≤ 0.05). C. Hematoxylin and eosin-stained sections taken from different part of lymph nodes and lungs (10× and 20× images are shown).