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Tumor exosomal miR-3473b promotes the metastatic colonization of lung cancer cells by activating the nuclear factor-κB signaling pathway of local fibroblasts

ABSTRACT: Tumor-derived exosomes are key factors that mediate the communication between tumor cells and stromal cells. In this study, we demonstrated that there was an uptake of cancer-derived exosomes by lung fibroblasts both in vivo and in vitro, leading to upregulation of inflammatory genes in fibroblasts, such as Il-6, Ccl1, Ccl2, Ccl5 and Cxcl2. Further analysis indicated that exosomal miR-3473b-mediated suppression of Nfkbid caused the inflammatory cytokine secertion in fibroblasts and further resulted in B cells accumulation in lungs. Inhibition of miR-3473b blocked inflammatory cytokine genes such as IL-6 expression in lung fibroblasts and B cell accumulation in lung. We further demonstrated that the lung metastasis areas and numbers were significantly decreased by using B cell neutralizing antibodies, suggesting B cell may play an important role in establishment of tumor promoting microenvironment for metastatic cancers cells colonization in the lung. In the present study, we showed that intercellular crosstalk occurred between cancer cells and fibroblasts via cancer-derived exosomes. Moreover, inhibition of the NF-kB activation in fibroblasts and B cells accumulation may become a potential target for the prevention and treatment of lung cancer.

ORGANISM(S): Mus musculus

PROVIDER: GSE142584 | GEO | 2019/12/25

REPOSITORIES: GEO

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