Osteoprotegerin (OPG) - a potential new role in the regulation of endothelial cell phenotype and tumour angiogenesis?
Osteoprotegerin (OPG) - a potential new role in the regulation of endothelial cell phenotype and tumour angiogenesis?
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DOI：
10.1002/ijc.21606
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发表时间：
2006-04-15
影响因子：
6.4
通讯作者：
Holen, I
中科院分区：
文献类型：
--
作者：
Cross, SS;Yang, ZY;Holen, I
癌症的进展取决于肿瘤血液供应的建立，因此肿瘤血管生成已被确定为新的抗癌药物的主要目标。最近的报道表明，骨保护素（OPG）通过抑制肿瘤坏死因子（TNF）相关的凋亡诱导配体（TRAIL）的活性或参与内皮细胞存活的控制。OPG在人类肿瘤发展和血管生成中的作用目前尚不清楚。在目前的研究中，我们证明了OPG支持内皮细胞存活的能力，以及使用基质小管形成实验在体外形成索状结构的能力。对各种人类癌症的研究表明，59%的恶性肿瘤（n = 512）中内皮细胞表达OPG，而良性肿瘤和正常组织相关的内皮细胞中不表达OPG （n = 178）。在400例乳腺肿瘤中，内皮细胞OPG表达与高肿瘤分级和某些组织学类型相关。我们的数据显示，内皮细胞OPG在恶性肿瘤和非恶性组织中的表达存在明显的差异，这支持了该分子在肿瘤血管系统的发育和/或维持中的潜在生物学作用。这是第一个报道OPG在体外促血管生成作用的研究，以及OPG在肿瘤内皮细胞中的表达与人类肿瘤的临床病理数据的相关性。(c) 2005 Wiley-Liss。公司。
The progression of cancer depends on the establishment of a tumour blood supply, and therefore tumour angiogenesis has been identified as a major target for new anticancer agents. Recent reports have suggested that osteoprotegerin (OPG) is involved in the control of endothelial cell survival through the inhibition or the activity of tumour necrosis factor- (TNF) related apoptosisinducing ligand (TRAIL). The role of OPG in human tumour development and angiogenesis is currently unknown. In the present study we demonstrate the ability of OPG to support endothelial cell survival, as well as the formation of cord-like structures in vitro using a matrigel tubule formation assay. Investigation of various human cancers demonstrated endothelial OPG expression in 59% of malignant tumours (n = 512), but in contrast, OPG was absent in endothelial cells associated with benign tumours and normal tissues (n = 178). In a series of 400 breast tumours, endothelial OPG expression was associated with high tumour grade and certain histological types. Our data show a clear separation in endothelial OPG expression between malignant tumours and nonmalignant tissues, supporting a potential biological role for this molecule in the development and/or maintenance of the tumour vasculature. This is the first study to report the proangiogenic effects of OPG in vitro, as well as correlating expression of OPG by tumour endothelial cells with clinicopathological data in human tumours. (c) 2005 Wiley-Liss. Inc.