Plasma from cancer patients featuring a characteristic protein composition mediates protection against apoptosis.
By comparative proteome analysis we searched for characteristic alterations of human plasma accompanying neoplastic disease. We identified protein alterations in plasma of prostate-, lung-, and breast-cancer patients in comparison to controls, comprising elevated levels of fibrinogen gamma-chain dimer, degradation products of antiplasmin and laminin gamma-chain, and elevated levels of acute phase proteins. The latter proteins and laminin fragments have been described as anti-apoptotic factors. We raised the question whether these alterations may have any relevance for the regulation of apoptosis. In contrast to plasma derived from healthy donors, samples from prostate-, lung-, and breast-cancer patients selectively inhibited Fas- and staurosporine-induced apoptosis in Jurkat cells but remained ineffective upon UV light-induced apoptosis. These data suggested that inhibition occurred by extracellular interference with apoptosis induction. Supporting this hypothesis, we found that formation of the CD95 death-inducing signal complex was strongly inhibited in the presence of plasma from cancer patients.
Institute of Cancer Research, University of Vienna, 1090 Vienna, Austria.
Susanne
S
Vejda
Carsten
C
Posovszky
Sieglinde
S
Zelzer
Barbara
B
Peter
Editha
E
Bayer
Dieter
D
Gelbmann
Rolf
R
Schulte-Hermann
Christopher
C
Gerner
D017209:Apoptosis; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000097:blood; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000096:biosynthesis; D019281:Dimerization; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005340:Fibrinogen / Q000096:biosynthesis / Q000737:chemistry; D006801:Humans; D019169:Jurkat Cells; D007797:Laminin / Q000097:blood / Q000737:chemistry; D008175:Lung Neoplasms / Q000097:blood; D008297:Male; D013058:Mass Spectrometry; D009369:Neoplasms / Q000097:blood*; D011233:Precipitin Tests; D011471:Prostatic Neoplasms / Q000097:blood; D015398:Signal Transduction; D014466:Ultraviolet Rays; D000979:alpha-2-Antiplasmin / Q000096:biosynthesis / Q000737:chemistry; D019014:fas Receptor / Q000096:biosynthesis
D007797:Laminin; D000979:alpha-2-Antiplasmin; D019014:fas Receptor; C089141:laminin gamma 1; D005340:Fibrinogen; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases