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Tyrosine kinase inhibitors and interferon-α increase tunneling nanotube (TNT) formation and cell adhesion in chronic myeloid leukemia (CML) cell lines.
FASEB J 2020FJ

Abstract

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.

Authors+Show Affiliations

Centre for Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, Bergen, Norway. Animal Models and Retroviral Vaccines Section, Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.Centre for Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, Bergen, Norway. Department of Internal Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway.Centre for Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, Bergen, Norway. Department of Internal Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway.Department of Molecular Cell Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.Department of Internal Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway. KinN Therapeutics, Bergen, Norway.Department of Medical Genetics, Haukeland University Hospital, Bergen, Norway.Department of Medical Genetics, Haukeland University Hospital, Bergen, Norway.Department of Molecular Cell Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.Centre for Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, Bergen, Norway.Centre for Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, Bergen, Norway. Department of Internal Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31945226

Citation

Omsland, Maria, et al. "Tyrosine Kinase Inhibitors and Interferon-α Increase Tunneling Nanotube (TNT) Formation and Cell Adhesion in Chronic Myeloid Leukemia (CML) Cell Lines." FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology, 2020.
Omsland M, Andresen V, Gullaksen SE, et al. Tyrosine kinase inhibitors and interferon-α increase tunneling nanotube (TNT) formation and cell adhesion in chronic myeloid leukemia (CML) cell lines. FASEB J. 2020.
Omsland, M., Andresen, V., Gullaksen, S. E., Ayuda-Durán, P., Popa, M., Hovland, R., ... Gjertsen, B. T. (2020). Tyrosine kinase inhibitors and interferon-α increase tunneling nanotube (TNT) formation and cell adhesion in chronic myeloid leukemia (CML) cell lines. FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology, doi:10.1096/fj.201802061RR.
Omsland M, et al. Tyrosine Kinase Inhibitors and Interferon-α Increase Tunneling Nanotube (TNT) Formation and Cell Adhesion in Chronic Myeloid Leukemia (CML) Cell Lines. FASEB J. 2020 Jan 16; PubMed PMID: 31945226.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Tyrosine kinase inhibitors and interferon-α increase tunneling nanotube (TNT) formation and cell adhesion in chronic myeloid leukemia (CML) cell lines. AU - Omsland,Maria, AU - Andresen,Vibeke, AU - Gullaksen,Stein-Erik, AU - Ayuda-Durán,Pilar, AU - Popa,Mihaela, AU - Hovland,Randi, AU - Brendehaug,Atle, AU - Enserink,Jorrit, AU - McCormack,Emmet, AU - Gjertsen,Bjørn Tore, Y1 - 2020/01/16/ PY - 2018/09/27/received PY - 2019/12/18/revised PY - 2019/12/19/accepted PY - 2020/1/17/entrez PY - 2020/1/17/pubmed PY - 2020/1/17/medline KW - cell adhesion KW - chronic myeloid leukemia KW - interferon-α KW - tunneling nanotubes KW - tyrosine kinase inhibitors JF - FASEB journal : official publication of the Federation of American Societies for Experimental Biology JO - FASEB J. N2 - 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. SN - 1530-6860 UR - https://www.unboundmedicine.com/medline/citation/31945226/Tyrosine_kinase_inhibitors and_interferon-α_increase_tunneling_nanotube_(TNT)_formation_and_cell_adhesion_in_chronic_myeloid_leukemia_(CML)_cell_lines L2 - https://doi.org/10.1096/fj.201802061RR DB - PRIME DP - Unbound Medicine ER -