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

Daniela Schilling, Mathias Gehrmann, Claudia Steinem, Antonio De Maio, Alan G. Pockley, Michael Abend, Michael Molls, Gabriele Multhoff

Publikation: Beitrag in FachzeitschriftArtikelBegutachtung

90 Zitate (Scopus)

Abstract

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≥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 (EC50 of Hsp70=85 μg/ml) and hypoxic (EC50 of Hsp70=55 μg/ml) tumor cells. The radiation-induced tumor cell killing was significantly enhanced by the addition of Hsp70 protein (50 μg/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.

OriginalspracheEnglisch
Seiten (von - bis)2467-2477
Seitenumfang11
FachzeitschriftFASEB Journal
Jahrgang23
Ausgabenummer8
DOIs
PublikationsstatusVeröffentlicht - Aug. 2009
Extern publiziertJa

Fingerprint

Untersuchen Sie die Forschungsthemen von „Binding of heat shock protein 70 to extracellular phosphatidylserine promotes killing of normoxic and hypoxic tumor cells“. Zusammen bilden sie einen einzigartigen Fingerprint.

Dieses zitieren