title: Heat-shock protein 72 cell-surface expression on human lung carcinoma cells in associated with an increased sensitivity to lysis mediated by adherent natural killer cells.
abstract: The cell-surface expression patterns of major histocompatibility complex (MHC) class I, class II and heat-shock protein 72 (HSP72) molecules were measured on human lung (LX-1) and mammary (MX-1) carcinoma cells. No major differences were found in the MHC cell-surface expression pattern of both cell lines. However, they differ significantly in their capacity to express HSP72 on their cell surface. Under physiological conditions LX-1 cells express HSP72 molecules on more than 90% of the cells, whereas MX-1 cells exhibit no significant HSP72 cell-surface expression (less than 5%). These expression patterns remained stable in all further cell passages tested. The sensitivity to lysis mediated by an interleukin-2 (IL-2)-stimulated, adherent natural killer (NK) cell population could be correlated with the amount of cell-surface-expressed HSP72 molecules. By antibody-blocking studies, using HSP72-specific monoclonal antibody (mAb), a strong inhibition of lysis was only found with LX-1 cells but not with MX-1 cells. In contrast to the cell-surface expression, the cytoplasmic amount of HSP72 in MX-1 cells was twice as high compared to LX-1 cells under physiological conditions. After nonlethal heat-shock the rate of induction and the total cytoplasmic amounts of HSP72 were comparable in both cell lines. The clonogenic cell viability of LX-1 cells after incubation at temperatures ranging from 41 degrees C to 44 degrees C was significantly elevated compared to that of MX-1 cells. In conclusion we state the following: (i) HSP72 cell-surface expression on human carcinoma cells is independent of the cytoplasmic amount of HSP72; (ii) the cell-surface expression of HSP72 is associated with an increased sensitivity of tumor cells to lysis mediated by an IL-2-stimulated, adherent NK cell population; (iii) thermoresistance is not related to the cytoplasmic HSP72 level but might be related to the amount of HSP72 expressed on the cell surface.
authors.affiliation: GSF-National Research Centre for Environment and Health, Institute of Clinical Hematology, Munich, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Botzler
authors.forename: R
authors.initials: R
authors.lastname: Issels
authors.forename: G
authors.initials: G
authors.lastname: Multhoff
mesh_terms: D002448:Cell Adhesion / Q000502:physiology; D002452:Cell Count; D003602:Cytotoxicity, Immunologic; D005434:Flow Cytometry; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D008175:Lung Neoplasms / Q000276:immunology* / Q000378:metabolism*; D012680:Sensitivity and Specificity
chemical_list: D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II