Tunneling nanotube-mediated intercellular vesicle and protein transfer in the stroma-provided imatinib resistance in chronic myeloid leukemia cells.

摘要: Intercellular communication within the bone marrow niche significantly promotes leukemogenesis and provides protection of leukemic cells from therapy. Secreted factors, intercellular transfer mitochondria receptor–ligand interactions have been shown as mediators this protection. Here we report that tunneling nanotubes (TNTs)—long, thin membranous structures, which identified a novel mode cross-talk—are formed in presence stroma mediate cellular vesicles to cells. Importantly, transmission via TNTs stromal increases resistance tyrosine kinase inhibitor, imatinib. Using correlative light-electron microscopy electron tomography show contain vesicles, provide membrane continuity with cell bodies can be open-ended. Moreover, trans-SILAC studies reveal non-autonomous proteome showed specific sets proteins are transferred together cells, potential role survival adaptation. Altogether, our findings evidence for biological TNT-mediated vesicle exchange between implicating direct protein stroma-provided