title: Secreted β3-integrin enhances natural killer cell activity against acute myeloid leukemia cells.
abstract: Integrins are a large family of heterodimeric proteins that are involved in cell adhesion, migration, and proliferation. Integrin diversity and function is regulated by alternative splicing. Membrane-bound and truncated β3-integrins were shown to be key players in cancer metastasis. However, the immunomodulatory functions of the soluble (s) β3-integrin have not been investigated yet. In this study, we described a novel form of sβ3-integrin in acute myeloid leukaemia (AML) patients. Furthermore, we assessed the role of the sβ3-integrin in the modulation of natural killer (NK)-cell activity. Levels of sβ3-integrin were analysed in plasma samples of 23 AML patients and 26 healthy donors by ELISA. The capacity of sβ3-integrin to regulate NK cell activity was investigated using proliferation, cytokine secretion, and cytotoxicity assays. Circulating sβ3-integrin was detected in the plasma of 8 AML patients. NK cells showed significantly higher proliferation rates after stimulation with sβ3-integrin and IL-2, IL-15 (73%). Significant increases in the NK cells' secreted levels of TNF-α, IFN-γ were measured in presence of sβ3-integrin. In addition, sβ3-integrin caused the upregulation of Granzyme B transcripts levels as well as FasL expression levels in NK cells. Most importantly, significantly higher K562 or AML blast target cell lysis rates were observed when NK cells were exposed to sβ3-integrin. This study reports the identification of a novel sβ3-integrin in AML patients and provides novel insights into its role in the immunomodulation of NK cell activity.
authors.affiliation: Institute for Transfusion Medicine, Hannover Medical School, Hannover, Germany.
authors.forename: Younis
authors.initials: Y
authors.lastname: Skaik
authors.affiliation: Institute for Transfusion Medicine, Hannover Medical School, Hannover, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Vahlsing
authors.affiliation: Institute for Transfusion Medicine, Hannover Medical School, Hannover, Germany.
authors.forename: Lilia
authors.initials: L
authors.lastname: Goudeva
authors.affiliation: Institute for Transfusion Medicine, Hannover Medical School, Hannover, Germany.
authors.forename: Britta
authors.initials: B
authors.lastname: Eiz-Vesper
authors.affiliation: Institute for Transfusion Medicine, Hannover Medical School, Hannover, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Battermann
authors.affiliation: Institute for Transfusion Medicine, Hannover Medical School, Hannover, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Blasczyk
authors.affiliation: Institute for Transfusion Medicine, Hannover Medical School, Hannover, Germany.
authors.forename: Constança
authors.initials: C
authors.lastname: Figueiredo
mesh_terms: D049109:Cell Proliferation; D016207:Cytokines / Q000276:immunology; D053222:Fas Ligand Protein / Q000235:genetics; D015973:Gene Expression Regulation, Leukemic; D053804:Granzymes / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D039661:Integrin beta3 / Q000097:blood / Q000276:immunology*; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D015470:Leukemia, Myeloid, Acute / Q000097:blood / Q000235:genetics / Q000276:immunology*; D020033:Protein Isoforms / Q000097:blood / Q000276:immunology; D015533:Transcriptional Activation; D015854:Up-Regulation
chemical_list: D016207:Cytokines; D053222:Fas Ligand Protein; D039661:Integrin beta3; D020033:Protein Isoforms; D053804:Granzymes