Evidence for a proangiogenic activity of TNF-related apoptosis-inducing ligand
Evidence for a proangiogenic activity of TNF-related apoptosis-inducing ligand
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DOI：
10.1593/neo.03421
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发表时间：
2004-07-01
期刊：
影响因子：
4.8
通讯作者：
Zauli, G
中科院分区：
文献类型：
--
作者：
Secchiero, P;Gonelli, A;Zauli, G
肿瘤坏死因子相关凋亡诱导配体（TRAIL）/Apo-2L蛋白在一些高度血管化的软组织肉瘤的恶性细胞和炎性细胞中表达，从这一观察出发，在一系列体外试验中研究了TRAIL的血管生成潜力。重组可溶性TRAIL诱导的内皮细胞迁移和血管管形成的程度与血管内皮生长因子（VEGF），最好的特点的血管生成因子之一。然而，TRAIL的促血管生成活性不是由VEGF的内源性表达介导的。尽管TRAIL增强VEGF诱导的细胞外信号调节激酶（ERK）磷酸化和内皮细胞增殖，但TRAIL + VEGF的组合在诱导血管管形成方面与单独的VEGF相比没有显示出累加效应。因此，尽管TRAIL因其在多种癌细胞中诱导凋亡的能力而作为潜在的抗癌治疗剂而受到关注，但我们目前的数据表明，TRAIL也可能在促进血管生成方面发挥意想不到的作用，这可能具有治疗意义。
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.