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Schilling, D. ; Gehrmann, M. ; Steinem, C.* ; de Maio, A.* ; Pockley, A.G.* ; Abend, M.* ; Molls, M. ; Multhoff, G.

Binding of heat shock protein 70 to extracellular phosphatidylserine promotes killing of normoxic and hypoxic tumor cells.

FASEB J. 23, 2467-2477 (2009)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Hypoxia is well known to limit curability of tumors by ionizing radiation. Here, we show that hypoxia treatment of tumor cells causes coexpression of heat shock protein 70 (Hsp70) and phosphatidylserine (PS) on the cell surface. Colocalization of Hsp70 and PS, as determined by confocal microscopy, also occurs when exogenous FITC-labeled Hsp70 protein is added to normoxic and hypoxic tumor cells. Moreover, the interaction of Hsp70 with PS was demonstrated in artificial unilamellar phosphatidylcholine/ phosphatidylserine (PC/PS) liposomes at the physiological ratio of 8/2. Indeed, the Hsp70-liposome interaction gradually increased with elevating PS molar ratios (8/2 > or = 7/3 < 5/5 < 4/6 < 3/7 < 2/8). In contrast, only a weak Hsp70 interaction was detected in phosphatidylcholine/phosphatidylglycerol (PC/PG) liposomes, thus demonstrating that the interaction was not a charge-related effect. The interaction of Hsp70 with surface PS significantly reduces clonogenic cell survival in normoxic (EC(50) of Hsp70=85 microg/ml) and hypoxic (EC(50) of Hsp70=55 microg/ml) tumor cells. The radiation-induced tumor cell killing was significantly enhanced by the addition of Hsp70 protein (50 microg/ml). Since apoptosis was not significantly enhanced in normoxic and hypoxic tumor cells by the addition of Hsp70, we hypothesize that the Hsp70 protein-induced reduction in clonogenic cell survival might be through necrosis rather than apoptosis.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords nonapoptotic tumor cell death; stress proteins; ionizing radiation; cancer therapy; heat-shock proteins; natural-killer-cells; immune-response; molecular chaperones; transcription factor; mammalian-cells; stress-proteins; in-vitro; hsp70; cancer
ISSN (print) / ISBN 0892-6638
e-ISSN 1530-6860
Journal FASEB Journal
Quellenangaben Volume: 23, Issue: 8, Pages: 2467-2477 Article Number: , Supplement: ,
Publisher Wiley
Publishing Place Bethesda, Md.
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) CCG Innate Immunity in Tumor Biology (PATH-KTB)