Tyrosine kinase inhibitors and interferon‐α increase tunneling nanotube (TNT) formation and cell adhesion in chronic myeloid leukemia (CML) cell lines (
| Autor: | Emmet McCormack, Stein-Erik Gullaksen, Mihaela Popa, Vibeke Andresen, Atle Brendehaug, Randi Hovland, Pilar Ayuda-Durán, Bjørn Tore Gjertsen, Jorrit M. Enserink, Maria Omsland |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Immunoblotting Fluorescent Antibody Technique Cell Communication Biochemistry 03 medical and health sciences Mice 0302 clinical medicine Cell Line Tumor Leukemia Myelogenous Chronic BCR-ABL Positive hemic and lymphatic diseases Genetics medicine Cell Adhesion Animals Humans Molecular Biology Protein Kinase Inhibitors Cells Cultured Chemistry Integrin beta1 Myeloid leukemia Interferon-alpha Imatinib Xenograft Model Antitumor Assays 030104 developmental biology medicine.anatomical_structure Nilotinib Cell culture Cancer research Microscopy Electron Scanning Female Bone marrow Stem cell K562 Cells Tyrosine kinase 030217 neurology & neurosurgery Biotechnology medicine.drug K562 cells |
| Zdroj: | The FASEB Journal |
| ISSN: | 3774-3791 |
| Popis: | Chronic myeloid leukemia (CML) is a stem cell disease of the bone marrow where mechanisms of inter‐leukemic communication and cell‐to‐cell interactions are proposed to be important for optimal therapy response. Tunneling nanotubes (TNTs) are novel intercellular communication structures transporting different cargos with potential implications in therapy resistance. Here, we have investigated TNTs in CML cells and following treatment with the highly effective CML therapeutics tyrosine kinase inhibitors (TKIs) and interferon‐α (IFNα). CML cells from chronic phase CML patients as well as the blast crisis phase cell lines, Kcl‐22 and K562, formed few or no TNTs. Treatment with imatinib increased TNT formation in both Kcl‐22 and K562 cells, while nilotinib or IFNα increased TNTs in Kcl‐22 cells only where the TNT increase was associated with adherence to fibronectin‐coated surfaces, altered morphology, and reduced movement involving β1integrin. Ex vivo treated cells from chronic phase CML patients showed limited changes in TNT formation similarly to bone marrow cells from healthy individuals. Interestingly, in vivo nilotinib treatment in a Kcl‐22 subcutaneous mouse model resulted in morphological changes and TNT‐like structures in the tumor‐derived Kcl‐22 cells. Our results demonstrate that CML cells express low levels of TNTs, but CML therapeutics increase TNT formation in designated cell models indicating TNT functionality in bone marrow derived malignancies and their microenvironment. publishedVersion |
| Databáze: | OpenAIRE |
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