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Prostate Adenocarcinoma Cells Release the Novel Proinflammatory Polypeptide EMAP-II in Response to Stress¹

University of Nottingham Laboratory of Molecular Oncology, Cancer Research Campaign Department of Clinical Oncology, City Hospital, Nottingham NG5 1PB, United Kingdom

The proinflammatory protein endothelial monocyte-activating polypeptide II (EMAP-II) was first detected in supernatants of murine tumor cells by virtue of its ability to stimulate endothelial-dependent coagulation in vitro. The purified protein has pleiotropic effects on endothelial cells, monocytes, and neutrophils; however, its function in vivo is unknown, and the mechanism whereby it is released from cells is poorly understood. We investigated the expression of EMAP-II in human prostate adenocarcinoma specimens by immunohistochemistry and in LNCaP and DU-145 human prostate adenocarcinoma cells by reverse transcription-PCR, flow cytometry, and Western blotting. We then examined the effects of chemical and physiological stress on release and processing of EMAP-II by LNCaP and DU-145 cells. These cells constitutively 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 induces the release of the M_r 34,000 form and further processing to the M_r 27,000 and M_r 22,000 forms. Hypoxia, but not heat shock, is a potent inducer of 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 constitutive hypoxia may potentiate the effects of those agents through the localized activation of host effector mechanisms.

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