Omsland Maria, Bruserud Øystein, Gjertsen Bjørn T, Andresen Vibeke
Centre for Cancer Biomarkers CCBIO, Department of Clinical Science, Precision Oncology Research Group, University of Bergen, Bergen, Norway.
Leukaemia Research Group, Department of Clinical Science, University of Bergen, Bergen, Norway.
Oncotarget. 2017 Jan 31;8(5):7946-7963. doi: 10.18632/oncotarget.13853.
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.
急性髓系白血病（AML）是一种源自骨髓的血癌，白血病骨髓中的细胞间通讯参与疾病的发生、发展和化疗耐药。隧道纳米管（TNTs）是参与细胞内容物和病原体运输的细胞间通讯结构，也被证明在细胞死亡调节和化疗耐药中发挥作用。在这里，我们通过实时荧光显微镜研究了TNTs的存在，并在原代AML细胞和AML细胞系中鉴定了TNT的形成。我们发现NF-κB活性参与TNT的调节和形成。阿糖胞苷下调TNTs，并单独或与柔红霉素联合抑制NF-κB，为NF-κB途径参与TNT形成提供了额外支持。有趣的是，发现柔红霉素定位于连接AML细胞的TNTs中的溶酶体，表明TNTs作为药物运输装置的新功能。我们得出结论，TNT通讯可能反映了AML的重要生物学特征，可在未来的治疗开发中进行探索。
