Heat-shock protein 72 cell-surface expression on human lung carcinoma cells is associated with an increased sensitivity to lysis mediated by adherent natural killer cells |
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Authors: | Claus Botzler Rolf Issels G Multhoff |
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Institution: | University Hospital Gro?hadern, LMU Munich, Med. Klinik III, Marchioninistrasse 15, 81377 Munich, Germany, DE GSF - National Research Centre for Environment and Health, Institute of Clinical Hematology, Marchioninistrasse 25, 81377 Munich, Germany, Fax: 089 7099 400, DE
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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°C to 44°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 tumour 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.
Received: 20 June 1996 / Accepted: 25 September 1996 |
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Keywords: | Carcinoma Heat-shock protein 72 (HSP72) Adherent NK cells Immune response Thermoresistance |
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