title: Tunneling nanotube (TNT) formation is downregulated by cytarabine and NF-κB inhibition in acute myeloid leukemia (AML).
abstract: Acute myeloid leukemia (AML) is a bone marrow derived blood cancer where intercellular communication in the leukemic bone marrow participates in disease development, progression and chemoresistance. Tunneling nanotubes (TNTs) are intercellular communication structures involved in transport of cellular contents and pathogens, also demonstrated to play a role in both cell death modulation and chemoresistance. Here we investigated the presence of TNTs by live fluorescent microscopy and identified TNT formation between primary AML cells and in AML cell lines. We found that NF-κB activity was involved in TNT regulation and formation. Cytarabine downregulated TNTs and inhibited NF-κB alone and in combination with daunorubicin, providing additional support for involvement of the NF-κB pathway in TNT formation. Interestingly, daunorubicin was found to localize to lysosomes in TNTs connecting AML cells indicating a novel function of TNTs as drug transporting devices. We conclude that TNT communication could reflect important biological features of AML that may be explored in future therapy development.
authors.affiliation: Centre for Cancer Biomarkers CCBIO, Department of Clinical Science, Precision Oncology Research Group, University of Bergen, Bergen, Norway.
authors.forename: Maria
authors.initials: M
authors.lastname: Omsland
authors.affiliation: Leukaemia Research Group, Department of Clinical Science, University of Bergen, Bergen, Norway.|Department of Internal Medicine, Haematology Section, Haukeland University Hospital, Bergen, Norway.
authors.forename: Øystein
authors.initials: Ø
authors.lastname: Bruserud
authors.affiliation: Centre for Cancer Biomarkers CCBIO, Department of Clinical Science, Precision Oncology Research Group, University of Bergen, Bergen, Norway.|Department of Internal Medicine, Haematology Section, Haukeland University Hospital, Bergen, Norway.
authors.forename: Bjørn T
authors.initials: BT
authors.lastname: Gjertsen
authors.affiliation: Centre for Cancer Biomarkers CCBIO, Department of Clinical Science, Precision Oncology Research Group, University of Bergen, Bergen, Norway.
authors.forename: Vibeke
authors.initials: V
authors.lastname: Andresen
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D001692:Biological Transport; D002450:Cell Communication / Q000187:drug effects*; D003561:Cytarabine / Q000494:pharmacology*; D003630:Daunorubicin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D018922:HL-60 Cells; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D043942:Nanotubes; D015398:Signal Transduction / Q000187:drug effects; D000074084:THP-1 Cells; D014407:Tumor Cells, Cultured
chemical_list: D016328:NF-kappa B; D003561:Cytarabine; D003630:Daunorubicin
keywords: NF-κB; acute myeloid leukemia; cell-to-cell communication; chemotherapeutics; tunneling nanotubes