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 ave involved in intracellular antigen processing and the pre sentation of cell-membrane-anchored antigens. We show that non-lethal heat shock (41.8 degrees C) causes comparable rates of HSP72 (about 20 x) and HSP73 (about 3x) synthesis in both tumor (including human Ewing 's sarcoma, ES and osteosarcoma cells, HOS58) and normal cells (includ ing EBV-transformed B-LCL, PBL and fibroblasts derived from healthy hu man volunteers). However, following non-lethal heat stress and a recov ery period at 37 degrees C, now cytometric analysis with a specific MA b 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 H SP72-specific MAb. In addition, co-incubation of untreated tumor cells with supernatants from lethally heat-shocked cells, which contain HSP 72, did not lead to HSP72 cell-surface expression. Thus, non-specific association of HSP72 molecules with the outer plasma membrane is unlik ely. In conclusion, despite comparable cytoplasmic HSP72 induction, hu man tumor cells differ from normal cells in their capacity to express HSP72 on their surface. This might imply clinical application as a mea ns to target a stress-inducible, tumor-specific immune response. (C) 1 995 Wiley-Liss, Inc.