Apoptosis

, 11:2137

EMAP-II facilitates TNF-R1 apoptotic signalling in endothelial cells and induces TRADD mobilization

Authors

  • Remco van Horssen
    • Laboratory of Experimental Surgical Oncology, Department of Surgical Oncology3000 Daniel den Hoed Cancer Centre
    • Department of Cell BiologyNCMLS, Radboud University Medical Centre
  • Joost A. P. Rens
    • Laboratory of Experimental Surgical Oncology, Department of Surgical Oncology3000 Daniel den Hoed Cancer Centre
  • Debby Schipper
    • Laboratory of Experimental Surgical Oncology, Department of Surgical Oncology3000 Daniel den Hoed Cancer Centre
  • Alexander M. M. Eggermont
    • Laboratory of Experimental Surgical Oncology, Department of Surgical Oncology3000 Daniel den Hoed Cancer Centre
    • Laboratory of Experimental Surgical Oncology, Department of Surgical Oncology3000 Daniel den Hoed Cancer Centre
Article

DOI: 10.1007/s10495-006-0284-5

Cite this article as:
Horssen, R.v., Rens, J.A.P., Schipper, D. et al. Apoptosis (2006) 11: 2137. doi:10.1007/s10495-006-0284-5

Abstract

Endothelial monocyte-activating polypeptide-II (EMAP-II), a proinflammatory cytokine with antiangiogenic properties, renders tumours sensitive to tumour necrosis factor-alpha (TNF) treatment. The exact mechanisms for this effect remain unclear. Here we show that human endothelial cells (EC) are insensitive to TNF-induced apoptosis but after a short pre-treatment with EMAP-II, EC quickly undergo TNF-induced apoptosis. We further analysed this EMAP-II pre-treatment effect and found no increase of TNF-R1 protein expression but rather an induction of TNF-R1 redistribution from Golgi storage pools to cell membranes. In addition, we observed EMAP-II induced mobilization and membrane expression of the TNF-R1-Associated Death Domain (TRADD) protein. Immunofluorescence co-staining experiments revealed that these two effects occurred at the same time in the same cell but TNF-R1 and TRADD were localized in different vesicles. These findings suggest that EMAP-II sensitises EC to apoptosis by facilitating TNF-R1 apoptotic signalling via TRADD mobilization and introduce a molecular and antiangiogenic explanation for the TNF sensitising properties of EMAP-II in tumours.

Keywords

ApoptosisEndothelial cellsEMAP-IITNF-R1TRADD

Copyright information

© Springer Science + Business Media, LLC 2006