TY - JOUR T1 - Tunneling nanotubes contribute to the stroma-mediated imatinib resistance of leukemic cells JF - bioRxiv DO - 10.1101/425041 SP - 425041 AU - Marta D. Kolba AU - Wioleta Dudka AU - Monika Zaręba-Kozioł AU - Agata Kominek AU - Paolo Ronchi AU - Laura Turos AU - Jakub Wlodarczyk AU - Yannick Schwab AU - Dominik Cysewski AU - Katja Srpan AU - Daniel M. Davis AU - Katarzyna Piwocka Y1 - 2018/01/01 UR - http://biorxiv.org/content/early/2018/09/25/425041.abstract N2 - Intercellular communication within the bone marrow niche significantly influences leukemogenesis and the sensitivity of leukemic cells to therapy. Tunneling nanotubes (TNTs) are a novel mode of intercellular cross-talk. They are long, thin membranous protrusions that enable the direct transfer of various cargo between cells. Here we show that TNTs are formed between leukemic and bone marrow stromal cells. Fluorescence confocal microscopy with 3D reconstructions, correlative light-electron microscopy and electron tomography provided evidence that TNTs transfer cellular vesicles between cells. The quantitative analysis demonstrated that the stromal cells stimulate TNT-mediated vesicle transfer towards leukemic cells. Transfer of vesicular cargo from stromal cells correlated with increased resistance to anti-leukemic treatment. Moreover, specific sets of proteins with a potential role in survival and the drug response were transferred within these vesicles. Altogether, we found that TNTs are involved in the leukemia-stroma cross-talk and the stroma-mediated cytoprotection of leukemic cells. Our findings implicate TNT connections as a possible target for therapeutic interventions within the leukemia microenvironment to attenuate stroma-conferred protection. ER -