Tunneling nanotubes contribute to the stroma-mediated imatinib resistance of leukemic cells

ABSTRACT: Intercellular communication within the bone marrow niche significantly influences leukemogenesis and the sensitivity of leukemic cells to therapy. However, the landscape of possible cell-cell interactions is still incomplete. Tunneling nanotubes (TNTs) are a novel mode of intercellular cross-talk. They are long, thin membranous conduits that enable the direct transfer of various cargo between cells. The present study found that TNTs are formed between leukemic and bone marrow stromal cells. Confocal three-dimensional reconstructions, correlative light-electron microscopy, and electron tomography provided evidence that TNTs transfer cellular vesicles between cells. The quantitative analysis demonstrated the stimulation of TNT-mediated vesicle transfer from stromal cells to leukemic cells by the stromal component. The vesicular cargo that was received from stroma cells conferred 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 a novel and potent mechanism that participates in 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.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Bone Marrow

SUBMITTER: Dominik Cysewski  

LAB HEAD: Katarzyna Piwocka

PROVIDER: PXD011013 | Pride | 2022-02-16

REPOSITORIES: Pride