Synergistic effects of heat and ET-18-OCH3 on membrane expression of hsp70and lysis of leukemic K562 cells

Citation
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
Citations number
42
Categorie Soggetti
Cardiovascular & Hematology Research
Journal title
EXPERIMENTAL HEMATOLOGY
ISSN journal
0301472X → ACNP
Volume
27
Issue
3
Year of publication
1999
Pages
470 - 478
Database
ISI
SICI code
0301-472X(199903)27:3<470:SEOHAE>2.0.ZU;2-H
Abstract
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.