Angiopoietin-like 4 is a proangiogenic factor produced during ischemia and in conventional renal cell carcinoma
Angiopoietin-like 4 is a proangiogenic factor produced during ischemia and in conventional renal cell carcinoma
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DOI：
10.1016/s0002-9440(10)64285-x
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发表时间：
2003-05-01
影响因子：
6
通讯作者：
Germain, S
中科院分区：
文献类型：
--
作者：
Le Jan, S;Amy, C;Germain, S
与正常组织相比，缺血和实体肿瘤组织的血流灌注较差，导致代谢变化和慢性缺氧，进而促进血管生成。我们发现人血管生成素样蛋白4(ANGPTL4)是一个低氧诱导内皮细胞表达的基因。我们发现，ANGPTL4的mRNA和蛋白水平都随着低氧的反应而增加。当在鸡绒毛膜尿囊膜实验中测试时，ANGPTL4诱导了强烈的促血管生成反应，不依赖于血管内皮生长因子。在人类病理学中，在严重的腿部缺血等条件下，ANGPTL4 mRNA在缺血组织中产生。在肿瘤中，ANGPTL4产生于坏死区周围的缺氧区。我们观察到在常规肾细胞癌的肿瘤细胞中ANGPTL4的mRNA水平特别高。其他良性和恶性肾肿瘤细胞不产生ANGPTL4 mRNA。因此，这种分子似乎是传统肾癌的一个标志。ANGPTL4最初被认为是一个过氧化物酶体增殖物激活受体α和伽马靶基因，有可能作为一种新的诊断工具和潜在的治疗靶点，调节肿瘤和缺血组织中的血管生成。这项研究还表明，ANGPTL4可能在代谢紊乱和缺氧诱导的血管生成之间提供了联系。
Ischemic and solid tumor tissues are less well perfused than normal tissue, leading to metabolic changes and chronic hypoxia, which in turn promotes angiogenesis. We identified human angiopoietin-like 4 (angptl4) as a gene with hypoxia-induced expression in endothelial cells. We showed that the levels of both mRNA and protein for ANGPTL4 increased in response to hypoxia. When tested in the chicken chorioallantoic membrane assay, ANGPTL4 induced a strong proangiogenic response, independently of vascular endothelial growth factor. In human pathology, ANGPTL4 mRNA is produced in ischemic tissues, in conditions such as critical leg ischemia. In tumors, ANGPTL4 is produced in the hypoxic areas surrounding necrotic regions. We observed particularly high levels of ANGPTL4 mRNA in tumor cells of conventional renal cell carcinoma. Other benign and malignant renal tumor cells do not produce ANGPTL4 mRNA. This molecule therefore seems to be a marker of conventional renal cell carcinoma. ANGPTL4, originally identified as a peroxisome proliferator-activated receptor alpha and gamma target gene, has potential for use as a new diagnostic tool and a potential therapeutic target, modulating angiogenesis both in tumors and in ischemic tissues. This study also suggests that ANGPTL4 may provide a link between metabolic disorders and hypoxia-induced angiogenesis.