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

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...

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Bibliographic Details
Published in:Neoplasia (New York, N.Y.) N.Y.), 2004-07, Vol.6 (4), p.364-373
Main Authors: Secchiero, Paola, Gonelli, Arianna, Carnevale, Edvige, Corallini, Federica, Rizzardi, Clara, Zacchigna, Serena, Melato, Mauro, Zauli, Giorgio
Format: Article
Language:English
Subjects:
angiogenesis
Apoptosis
Apoptosis Regulatory Proteins
Cell Differentiation
Cell Movement - drug effects
Cells, Cultured
endothelial cells
Endothelium, Vascular - cytology
Endothelium, Vascular - drug effects
Endothelium, Vascular - physiology
Humans
Membrane Glycoproteins - pharmacology
Membrane Glycoproteins - physiology
Neoplasm Invasiveness
Neovascularization, Pathologic - pathology
Sarcoma - blood supply
Sarcoma - pathology
Sarcoma - physiopathology
signal transduction
TNF-Related Apoptosis-Inducing Ligand
TRAIL
Tumor Cells, Cultured
Tumor Necrosis Factor-alpha - pharmacology
Tumor Necrosis Factor-alpha - physiology
Umbilical Veins
Vascular Endothelial Growth Factor A - pharmacology
VEGF
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Summary: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.
ISSN:1476-5586
1522-8002
1476-5586
1522-8002
DOI:10.1593/neo.03421