C. Botzler et al., Synergistic effects of heat and ET-18-OCH3 on membrane expression of hsp70and lysis of leukemic K562 cells, EXP HEMATOL, 27(3), 1999, pp. 470-478
We previously reported that cell surface expression of hsp70, the major str
ess inducible member of the 70-kDa heat shock protein family, is inducible
by nonlethal heat as well as by treatment with the membrane-interactive com
pound alkyl-lysophospholipid 1-octadecyl-2-methyl-rac-glycero-3-phosphochol
ine (ET-18-OCH3) selectively on human tumor cell lines. Plasma membrane exp
ression of hsp70 increases selectively the sensitivity of tumor cells to ly
sis and, therefore, might play an important role in the antitumor immune re
sponse. Here, we demonstrate that a combined treatment consisting of sublet
hal heat (41.8 degrees C) and a noncytotoxic concentration of ET-18-OCH3 (2
5 mu g/mL) results in a synergistic increase in the amount of cell membrane
-bound hsp70 on leukemic K562 cells and on freshly isolated bone marrow of
a chronic myelogeneous leukemia (CML) patient, but not on peripheral blood
lymphocytes or CD34(+) hematopoietic progenitor cells of healthy human indi
viduals. Under these conditions the repopulating capacity of progenitor cel
ls was not influenced. The increased hsp70 membrane expression on leukemic
K562 cells results in a significantly increased sensitivity to lysis mediat
ed by natural killer cells. In contrast to leukemic cells, the lysis of per
ipheral blood lymphocytes and CD34(+) progenitor cells that lack expression
of hsp70 on their plasma membrane was not negatively influenced by this tr
eatment. A nonspecific disruption of the plasma membrane could be excluded,
because treatment with a nontoxic concentration of the detergent Tween20 d
id not have an influence on hsp70 cell surface expression or on the sensiti
vity to lysis, Our findings might have further clinical implications,vith r
espect to purging of bone marrow from patients suffering from leukemia at s
ublethal conditions to induce a tumor-selective immune response, (C) 1999 I
nternational Society for Experimental Hematology, Published by Elsevier Sci
ence Inc.