Involvement of endothelial monocyte activating polypeptide II in tumor necrosis factor-alpha-based anti-cancer therapy

In 1990 Clauss et al. first reported on a 44-kDa polypeptide, later called Endothelial Monocyte Activating Polypeptide II (EMAP II). This protein was discovered in the supernatant of Meth-A fibrosarcoma cells and was shown to enhance the induction of the procoagulant Tissue Factor (TF) on endothelial cells. Besides up-regulation of TF mRNA, EMAP II increases cellular receptors for TNF on endothelial cells, which is likely to enhance the predisposition of tumors to undergo thrombosis and hemorrhagic necrosis, once challenged with TNF. This feature enables EMAP II to upregulate the TNF sensitivity of TNF-resistant tumors, an observation of importance in developing new approaches aimed at improving the efficacy of TNF as an anticancer treatment. We describe the potential additional effects of EMAP II, when used in combination with TNF, with regards to antitumor activity in the Isolated Limb Perfusion (ILP) setting. In addition, we describe our experimental data in human sarcoma, which also supports this hypothesis.