CD13/APN is activated by angiogenic signals and is essential for capillary tube formation
CD13/APN is activated by angiogenic signals and is essential for capillary tube formation
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DOI：
10.1182/blood.v97.3.652
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发表时间：
2001-02-01
期刊：
影响因子：
20.3
通讯作者：
Shapiro, LH
中科院分区：
文献类型：
--
作者：
Bhagwat, SV;Lahdenranta, J;Shapiro, LH
在造血区室中，CD 13/APN金属蛋白酶是定向于骨髓谱系的细胞的最早标志物之一，其中它仅在骨髓祖细胞及其分化后代的表面上表达。CD 13/APN也存在于非造血组织中，并且最近描述了其在血管生成但非正常血管系统的内皮细胞上的新表达。用CD 13/APN抑制剂治疗动物显著损害视网膜新生血管形成、绒毛尿囊膜血管生成和异种移植肿瘤生长，表明CD 13/APN在血管发生中起重要的功能作用，并将其鉴定为血管生成的关键调节剂。为了研究肿瘤血管中CD 13/APN诱导的机制，研究了促进血管生成进展的因素对CD 13/APN的调节。在本报告中，显示了在原代细胞和细胞系中内源性CD 13/APN水平响应于缺氧、血管生成生长因子和调节血管生成期间毛细血管形成的信号而上调。报告人的文字记录;含有CD 13/APN近端启动子序列的质粒在对调节内源基因表达的相同血管生成信号的应答中和在人肿瘤异种移植物中显著增加，表明该片段含有对CD 13/APN表达的血管生成诱导必需的元件。最后，CD 13/APN的功能性拮抗剂干扰原代血管内皮细胞的管形成但不干扰增殖，提示CD 13/APN在内皮细胞形态发生的控制中起作用。这些研究清楚地确立了CD 13/APN金属蛋白酶作为血管生成过程中内皮形态发生的重要调节因子。(C)2001年，美国血液学会。
In the hematopoietic compartment, the CD13/APN metalloprotease is one of the earliest markers of cells committed to the myeloid lineage where it is expressed exclusively on the surface of myeloid progenitors and their differentiated progeny. CD13/APN is also found in nonhematopoietic tissues, and its novel expression on the endothelial cells of angiogenic, but not normal, vasculature was recently described, Treatment of animals with CD13/APN inhibitors significantly impaired retinal neovascularization, chorioallantoic membrane angiogenesis, and xenograft tumor growth, indicating that CD13/APN plays an important functional role in vasculogenesis and identifying it as a critical regulator of angiogenesis. To investigate the mechanisms of CD13/APN induction in tumor vasculature, the regulation of CD13/APN by factors contributing to angiogenic progression was studied, In this report, it is shown that endogenous CD13/APN levels in primary cells and cell lines are up-regulated in response to hypoxia, angiogenic growth factors, and signals regulating capillary tube formation during angiogenesis. Transcription of reporter; plasmids containing CD13/APN proximal promoter sequences is significantly increased in response to the same angiogenic signals that regulate the expression of the endogenous gene and in human tumor xenografts, indicating that this fragment contains elements essential for the angiogenic induction of CD13/APN expression, Finally, functional antagonists of CD13/APN interfere with tube formation but not proliferation of primary vascular endothelial cells, suggesting that CD13/APN functions in the control of endothelial cell morphogenesis. These studies clearly establish the CD13/APN metalloprotease as an important regulator of endothelial morphogenesis during angiogenesis. (C) 2001 by The American Society of Hematology.