Evidence for a proangiogenic activity of TNF-related apoptosis-inducing ligand

Paola Secchiero, Arianna Gonelli, Edvige Carnevale, Federica Corallini, Clara Rizzardi, Serena Zacchigna, Mauro Melato, Giorgio Zauli

Research output: Contribution to journalArticlepeer-review


Starting from the observation that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/Apo-2L protein is expressed in both malignant and inflammatory cells in some highly vascularized soft tissue sarcomas, the angiogenic potential of TRAIL was investigated in a series of in vitro assays. Recombinant soluble TRAIL induced endothelial cell migration and vessel tube formation to a degree comparable to vascular endothelial growth factor (VEGF), one of the best-characterized angiogenic factors. However, the proangiogenic activity of TRAIL was not mediated by endogenous expression of VEGF. Although TRAIL potentiated VEGF-induced extracellular signal-regulated kinase (ERK) phosphorylation and endothelial cell proliferation, the combination of TRAIL + VEGF did not show additive effects with respect to VEGF alone in inducing vessel tube formation. Thus, although TRAIL has gained attention as a potential anticancer therapeutic for its ability to induce apoptosis in a variety of cancer cells, our present data suggest that TRAIL might also play an unexpected role in promoting angiogenesis, which might have therapeutic implications.

Original languageEnglish
Pages (from-to)364-373
Number of pages10
JournalNeoplasia (United States)
Issue number4
Publication statusPublished - Jul 2004


  • Angiogenesis
  • Endothelial cells
  • Signal transduction
  • VEGF

ASJC Scopus subject areas

  • Cancer Research


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