Evidence of an immunologic mechanism behind the therapeutical effects of arsenic trioxide (As(2)O(3)) on myeloma cells.
Exposure of RPMI 8226, Karpas 707 and U266 human myeloma-like lines to low doses of As(2)O(3) was followed by a marked increase in lymphokine activated killers (LAK)-mediated killing and up- modulation of CD38 and CD54, two molecules involved in cell-cell interactions. Moreover, simultaneous exposure of effectors and targets to As(2)O(3) yielded the most effective condition for lysis. The expression of CD31 (CD38 ligand) and CD11a (CD54 ligand) was also up-regulated by LAK, suggesting that increased adhesion was responsible for the improved killing. Similar results were obtained using freshly isolated myeloma cells. These findings indicate that As(2)O(3) may be useful to boost the immune system against myelomas.
Laboratory of Cell Biology, Department of Biology, Genetics and Biochemistry, University of Torino Medical School, via Santena 19, 10126 Torino, Italy.
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S
Deaglio
D
D
Canella
G
G
Baj
A
A
Arnulfo
S
S
Waxman
F
F
Malavasi
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000187:drug effects / Q000378:metabolism; D000970:Antineoplastic Agents / Q000276:immunology / Q000627:therapeutic use; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000276:immunology* / Q000627:therapeutic use; D003602:Cytotoxicity, Immunologic; D004305:Dose-Response Relationship, Drug; D006131:Growth Inhibitors / Q000276:immunology / Q000627:therapeutic use; D006801:Humans; D016130:Immunophenotyping; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects / Q000378:metabolism; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D009244:NAD+ Nucleosidase / Q000187:drug effects / Q000378:metabolism; D010087:Oxides / Q000276:immunology* / Q000627:therapeutic use; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D000943:Antigens, Differentiation; D000970:Antineoplastic Agents; D001152:Arsenicals; D006131:Growth Inhibitors; D008562:Membrane Glycoproteins; D010087:Oxides; D018799:Intercellular Adhesion Molecule-1; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1; D000077237:Arsenic Trioxide