title: CD99 ligation upregulates HSP70 on acute lymphoblastic leukemia cells and concomitantly increases NK cytotoxicity.
abstract: CD99 is present in many human cell types, including high-level surface expression on pediatric B and T leukemias and Ewing tumors (ETs). On B lymphocytes and respective malignancies, its level decreases with the stage of maturation. Inter-individual variability of CD99 on B-cell precursor acute lymphoblastic leukemia (BCP-ALL) blasts was shown recently to be associated with distinct cytogenetic backgrounds. However, CD99 targets remain mainly unknown. Here, we show that administration of an anti-CD99 antibody to B- and T-leukemia cell lines induces heat shock protein 70 (HSP70), both on the cell surface and in the cytoplasm. Investigation of primary BCP-ALL cells rendered similar results. Intriguingly, CD99-induced modulation of HSP70 on ET cells had profiles different from that on leukemia cells. Since HSP70 expression on tumor cells is a prerequisite for natural killer (NK) cell-mediated tumor lysis, we hypothesized that CD99-induced HSP70 may allow targeting of some CD99-positive malignancies via NK-cell cytotoxicity. Our experiments with NK92 cell line demonstrated that leukemia cells with upregulated HSP70 can be successfully killed by effector cells. We consider our data as a new view of CD99 functions and as a basis for the development of a potential anti-tumor strategy based on heat-shock protein activation via CD99 triggering.
authors.affiliation: Department of Immunological Diagnostics, St. Anna Kinderkrebsforschung, Children's Cancer Research Institute, Vienna, Austria. zvenyslava.husak@ccri.at
authors.forename: Z
authors.initials: Z
authors.lastname: Husak
authors.forename: M N
authors.initials: MN
authors.lastname: Dworzak
mesh_terms: D000071443:12E7 Antigen; D015703:Antigens, CD / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000276:immunology*; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D015854:Up-Regulation
chemical_list: D000071443:12E7 Antigen; D015703:Antigens, CD; C061828:CD99 protein, human; D015815:Cell Adhesion Molecules; D018840:HSP70 Heat-Shock Proteins