Prostate adenocarcinoma cells release the novel proinflammatory polypeptide EMAP-II in response to stress

The proinflammatory protein endothelial monocyte-activating polypeptide II (EMAP-II) was first detected in supernatants of murine tumor cells by virtu e of its ability to stimulate endothelial-dependent coagulation in vitro. T he purified protein has pleiotropic effects on endothelial cells, monocytes , and neutrophils; however, its function in vivo is unknown, and the mechan ism whereby it is released from cells is poorly understood. We investigated the expression of EMAP-II in human prostate adenocarcinoma specimens by im munohistochemistry and in LNCaP and DU-145 human prostate adenocarcinoma ce lls by reverse transcription-PCR, flow cytometry, and Western blotting, We then examined the effects of chemical and physiological stress on release a nd processing of EMAP-II by LNCaP and DU-145 cells. These cells constitutiv ely express a M-r 34,000 form of EMAP-II that is retained intracellularly, Exposure to agents that induce apoptosis or, in some cases, necrosis induce s the release of the M-r 34,000 form and further processing to the M-r 27,0 00 and M-r 22,000 forms, Hypoxia, but not heat shock, is a potent inducer o f release and processing of biologically active EMAP-II by LNCaP and DU-145 cells. We suggest that release of EMAP-II by prostate adenocarcinoma cells as a consequence of treatment with anticancer agents or as a result of con stitutive hypoxia may potentiate the effects of those agents through the lo calized activation of host effector mechanisms.