A stress-inducible 72-kDa heat-shock protein (HSP72) is expressed on the surface of human tumor cells, but not on normal cells.
It is suggested that members of the heat-shock protein (HSP) 70 and 90 families are involved in intracellular antigen processing and the presentation of cell-membrane-anchored antigens. We show that non-lethal heat shock (41.8 degrees C) causes comparable rates of HSP72 (about 20x) and HSP73 (about 3x) synthesis in both tumor (including human Ewing's sarcoma, ES and osteosarcoma cells, HOS58) and normal cells (including EBV-transformed B-LCL, PBL and fibroblasts derived from healthy human volunteers). However, following non-lethal heat stress and a recovery period at 37 degrees C, flow cytometric analysis with a specific MAb showed HSP72 to be expressed only on the cell surface of tumor cells. The cell-surface localization of HSP72 was confirmed by Western-blot analysis of separated membranes and by immunoprecipitation with the HSP72-specific MAb. In addition, co-incubation of untreated tumor cells with supernatants from lethally heat-shocked cells, which contain HSP72, did not lead to HSP72 cell-surface expression. Thus, non-specific association of HSP72 molecules with the outer plasma membrane is unlikely. In conclusion, despite comparable cytoplasmic HSP72 induction, human tumor cells differ from normal cells in their capacity to express HSP72 on their surface. This might imply clinical application as a means to target a stress-inducible, tumor-specific immune response.
Multhoff
G
G
Forschungszentrum für Umwelt und Gesundheit, GSF-Institut für Klinische Hämatologie, Munich, Germany.
Botzler
C
C
Wiesnet
M
M
Müller
E
E
Meier
T
T
Wilmanns
W
W
Issels
R D
RD
D000818:Animals; D000911:Antibodies, Monoclonal; D015153:Blotting, Western; D005347:Fibroblasts / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000096:biosynthesis* / Q000276:immunology; D006361:Heating; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D008285:Major Histocompatibility Complex / Q000502:physiology; D008565:Membrane Proteins / Q000502:physiology; D009369:Neoplasms / Q000737:chemistry* / Q000276:immunology; D012513:Sarcoma, Experimental / Q000378:metabolism; D012680:Sensitivity and Specificity; D013312:Stress, Physiological / Q000209:etiology / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D008565:Membrane Proteins