title: KHYG-1 and NK-92 represent different subtypes of LFA-1-mediated NK cell adhesiveness.
abstract: Novel cancer cellular therapy approaches involving long-term ex vivo IL-2 stimulated highly cytotoxic natural killer (NK) cells are emerging. However, adhesion properties of such NK cells are not very well understood. Herein, we describe the novel observation of permanently activated alphaLbeta2 integrin leukocyte function-associated antigen (LFA)-1 adhesion receptor in long-term IL-2 activated NK cells and the permanent NK cell lines KHYG-1 and NK-92. We show that such cytokine activated NK effectors constitutively adhered to the LFA-1-ligand ICAM-1, whereas binding to the lower affinity ligand ICAM-3 required additional exogenous activating conditions. The results demonstrate an extended conformation and an intermediate affinity state for the LFA-1 population expressed by the NK cells. Interestingly, adhesion to ICAM-1 or K562 induced pronounced cell spreading in KHYG-1, but not in NK-92, and partially in long-term IL-2 stimulated primary NK cells. It is conceivable that such differential adhesion characteristics may impact motility potential of such NK effectors with relevance to clinical tumor targeting. KHYG-1 could be a useful model in planning future targeted therapeutic approaches involving NK effectors with augmented functions.
authors.affiliation: Blood Services Group, Health Sciences Authority, Singapore. garnet_suck@hsa.gov.sg
authors.forename: Garnet
authors.initials: G
authors.lastname: Suck
authors.forename: Suet-Mien
authors.initials: SM
authors.lastname: Tan
authors.forename: Sixian
authors.initials: S
authors.lastname: Chu
authors.forename: Madelaine
authors.initials: M
authors.lastname: Niam
authors.forename: Ardcharaporn
authors.initials: A
authors.lastname: Vararattanavech
authors.forename: Tsyr Jong
authors.initials: TJ
authors.lastname: Lim
authors.forename: Mickey B C
authors.initials: MB
authors.lastname: Koh
mesh_terms: D000704:Analysis of Variance; D000911:Antibodies, Monoclonal; D002448:Cell Adhesion / Q000502:physiology; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D005434:Flow Cytometry; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D007376:Interleukin-2 / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000502:physiology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism*; D018613:Microscopy, Confocal
chemical_list: D000911:Antibodies, Monoclonal; D007376:Interleukin-2; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1