Human endothelial precursor cells express tumor endothelial marker 1/endosialin/CD248
Human endothelial precursor cells express tumor endothelial marker 1/endosialin/CD248
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DOI：
10.1158/1535-7163.mct-08-0050
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发表时间：
2008-08-01
影响因子：
5.7
通讯作者：
Teicher, Beverly A.
中科院分区：
文献类型：
--
作者：
Bagley, Rebecca G.;Rouleau, Cecile;Teicher, Beverly A.
血管生成发生在正常生理过程以及肿瘤生长等病理条件下。基因表达谱的系列分析揭示了与正常成人内皮细胞相比，肿瘤内皮细胞中过度表达的基因[肿瘤内皮标志物 (TEM)]。由于在某些条件下恶性肿瘤的血管发育可能包括从骨髓中招募的内皮前体细胞（EPC），因此我们研究了EPC中的TEM表达。在源自人 CD133(+)/CD34(+) 细胞的血管内皮生长因子受体 2(+)/CD31(+)/CD45(-)/VE-钙粘蛋白(+) EPC 群体中发现了 TEM1 或内皮唾液酸蛋白 (CD248) 和其他 TEM 的表达。 EPC 与正常组织中完全分化的内皮细胞具有一些相同的特性，但逆转录 PCR 和流式细胞术显示 EPC 在分子和蛋白质水平上表达更高水平的内皮唾液酸蛋白。与成熟内皮细胞相比，EPC 中内皮唾液酸蛋白的表达升高表明内皮唾液酸蛋白参与肿瘤血管生成的早期阶段。抗内皮唾液酸蛋白抗体在体外抑制 EPC 迁移和管形成。在体内，免疫组织化学表明，在裸鼠体内建立的基质胶塞血管生成测定中，人EPC继续表达内皮唾液酸蛋白。以 25 mg/kg 全身递送的抗内皮唾液酸蛋白抗体也能够抑制皮下荷瘤裸鼠中的循环鼠 EPC。 SKNAS 肿瘤。先前已证明 EPC 和骨髓来源的细胞在某些情况下会融入恶性血管，但它们在该领域仍然存在争议。这里提供的有关在肿瘤脉管系统和 EPC 中上调的内皮基因的数据支持癌症中的血管生成过程可能涉及 EPC 的假设。
Angiogenesis occurs during normal physiologic processes as well as under pathologic conditions such as tumor growth. Serial analysis of gene expression profiling revealed genes [tumor endothelial markers (TEM)] that are overexpressed in tumor endothelial cells compared with normal adult endothelial cells. Because blood vessel development of malignant tumors under certain conditions may include endothelial precursor cells (EPC) recruited from bone marrow, we investigated TEM expression in EPC. The expression of TEM1 or endosialin (CD248) and other TEM has been discovered in a population of vascular endothelial growth factor receptor 2(+)/CD31(+)/CD45(-)/VE-cadherin(+) EPC derived from human CD133(+)/CD34(+) cells. EPC share some properties with fully differentiated endothelial cells from normal tissue, yet reverse transcription-PCR and flow cytometry reveal that EPC express higher levels of endosialin at the molecular and protein levels. The elevated expression of endosialin in EPC versus mature endothelial cells suggests that endosialin is involved in the earlier stages of tumor angiogenesis. Anti-endosialin antibodies inhibited EPC migration and tube formation in vitro. In vivo, immunohistochemistry indicated that human EPC continued to express endosialin protein in a Matrigel plug angiogenesis assay established in nude mice. Anti-endosialin antibodies delivered systemically at 25 mg/kg were also able to inhibit circulating murine EPC in nude mice bearing s.c. SKNAS tumors. EPC and bone marrow-derived cells have been shown previously to incorporate into malignant blood vessels in some instances, yet they remain controversial in the field. The data presented here on endothelial genes that are up-regulated in tumor vasculature and in EPC support the hypothesis that the angiogenesis process in cancer can involve EPC.