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Intercellular transfer of small RNAs from astrocytes to lung tumor cells induces resistance to chemotherapy.

ABSTRACT: Brain metastases are highly resistance to chemotherapy and have a poor prognosis for cure. Tumor cells are surrounded by activated astrocytes and exploit their cyto-protective properties for protection from apoptosis induced by chemotherapy. The mechanism by which astrocytes protect tumor cells is poorly understood. An important non-mutational mechanism of chemotherapy resistance is regulation of gene translation mediated by small non-coding RNAs (sRNAs), in particular, microRNAs (miRNAs). Here we studied the role of astrocytic sRNAs in promoting resistance of the human lung tumor PC14 cells to apoptosis induced by chemotherapy. To this end we compared the sRNA profile of human lung tumor cells that were cultured with or without astrocytes by miRNA microarray. The results show that sRNAs are transferred from astrocytes to PC14 cells in a contact-dependent manner. This transfer is fast and reached plateau already after six hours of co-culturing. Carbenoxolone, a broad-spectrum gap junction antagonist, inhibited the sRNAs transfer indicating that the sRNAs are transferred via gap-junction, maybe via survival pathways. Enforced expression of these sRNA in PC14 cells increased their resistance to the chemotherapy agent Taxol. In light of these results, we offer novel findings that may be clinically relevant to treatment development for brain metastases.

ORGANISM(S): synthetic construct Homo sapiens

PROVIDER: GSE72527 | GEO | 2018/08/31

REPOSITORIES: GEO

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Intercellular transfer of small RNAs from astrocytes to lung tumor cells induces resistance to chemotherapy.

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