Evidence for a Proangiogenic Activity of TNF-Related Apoptosis-Inducing Ligand

• Main Authors: Paola Secchiero, Arianna Gonelli, Edvige Carnevale, Federica Corallini, Clara Rizzardi, Serena Zacchigna, Mauro Melato, Giorgio Zauli
• Format: Article
• Language: English
• Published: Elsevier 2004-07-01
• Series: Neoplasia: An International Journal for Oncology Research
• Subjects: TRAIL; VEGF; signal transduction; angiogenesis; endothelial cells
• Online Access: http://www.sciencedirect.com/science/article/pii/S1476558604800824

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.