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. 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.
Secchiero
Paola
P
Human Anatomy Section, Department of Morphology and Embryology, University of Ferrara, Via Fossato di Mortara 66, Ferrara 44100, Italy.
Gonelli
Arianna
A
Carnevale
Edvige
E
Corallini
Federica
F
Rizzardi
Clara
C
Zacchigna
Serena
S
Melato
Mauro
M
Zauli
Giorgio
G
D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D002454:Cell Differentiation; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008562:Membrane Glycoproteins / Q000494:pharmacology / Q000502:physiology*; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000473:pathology*; D012509:Sarcoma / Q000098:blood supply / Q000473:pathology* / Q000503:physiopathology; D053221:TNF-Related Apoptosis-Inducing Ligand; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000502:physiology*; D014471:Umbilical Veins; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*
D051017:Apoptosis Regulatory Proteins; D008562:Membrane Glycoproteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A