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

Kolba, Marta and Dudka, Wioletta and Zaręba-Kozioł, Monika and Kominek, Agata and Ronchi, Paolo and Turos, Laura and Chroscicki, Piotr and Cysewski, Dominik and Piwocka, Katarzyna (2019) Tunneling nanotube-mediated intercellular vesicle and protein transfer in the stroma-provided imatinib resistance in chronic myeloid leukemia cells. Cell Death & Disease, 10 (11). pp. 1-16. ISSN Cell Death & Disease

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Official URL: https://www.nature.com/cddis/

Abstract

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

Item Type:Article
Subjects:Q Science > QH Natural history > QH301 Biology
Divisions:Mass Spectrometry Laboratory
ID Code:1827
Deposited By: Dominik Cysewski
Deposited On:06 Feb 2020 10:26
Last Modified:06 Feb 2020 10:26

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