IAP antagonization promotes inflammatory destruction of vascular endothelium by Axel Witt, Jens M Seeger, Oliver Coutelle, Paola Zigrino, Pia Broxtermann, Maria Andree, Kerstin Brinkmann, Christian Jüngst, Astrid C Schauss, Stephan Schüll, Dirk Wohlleber, Percy A Knolle, Martin Krönke, Cornelia Mauch, and Hamid Kashkar EMBO Rep. Volume ():e March 30, 2015 ©2015 by European Molecular Biology Organization

Comp A inhibits B16 melanoma growth in vivo Growth rates of B16 tumors mixed with matrigel and vehicle (control) or Comp A (2 μM) and subcutaneously injected into the flank region of recipient mice. Axel Witt et al. EMBO Rep. doi: /embr ©2015 by European Molecular Biology Organization

Comp A inhibits B16 tumor growth in vivo The murine melanoma cell line B16 was mixed with matrigel and vehicle (control) or Comp A (2 μM) and then subcutaneously injected into the flank region of recipient mice. Axel Witt et al. EMBO Rep. doi: /embr ©2015 by European Molecular Biology Organization

Comp A inhibits tumor vasculature in vivo B16 cells were mixed with matrigel and vehicle (control) or Comp A (2 μM) and subcutaneously injected into the flank region of recipient mice. Axel Witt et al. EMBO Rep. doi: /embr ©2015 by European Molecular Biology Organization

Comp A inhibits B16 tumor vasculature in vivo without altering immune cell infiltrationThe murine melanoma cell line B16 was mixed with matrigel and vehicle (control) or Comp A (2 μM) and then subcutaneously injected into the flank region of recipient mice... Axel Witt et al. EMBO Rep. doi: /embr ©2015 by European Molecular Biology Organization

Comp A promotes TNF ‐ induced endothelial cell death HUVEC and HDMEC cells were treated with increasing amounts of Comp A or Comp B alone or in combination with TNF (20 ng/ml). Axel Witt et al. EMBO Rep. doi: /embr ©2015 by European Molecular Biology Organization

Comp A promotes TNF ‐ induced endothelial cell death Measurement of clonogenicity of HUVEC cells treated as indicated. Axel Witt et al. EMBO Rep. doi: /embr ©2015 by European Molecular Biology Organization

Comp A potentiates TNF ‐ dependent vascular disruption in vivo A, BMatrigel was mixed with vehicle (control), Comp A (2 μM), or TNF (50 ng/ml) and subcutaneously injected into the flank region of recipient wild ‐ type mice (A) or TNFR ‐ 1/2−/− mice (B). Axel Witt et al. EMBO Rep. doi: /embr ©2015 by European Molecular Biology Organization

IAP antagonization potentiates TNF ‐ induced vascular disruption in vivoMatrigel was mixed with vehicle (control) or Comp A (2 μM) and subcutaneously injected into the flank region of recipient TNFR ‐ 1/2−/− mice. Axel Witt et al. EMBO Rep. doi: /embr ©2015 by European Molecular Biology Organization