A subpopulation of circulating endothelial cells express CD109 and is enriched in the blood of cancer patients.
A subpopulation of circulating endothelial cells express CD109 and is enriched in the blood of cancer patients.
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DOI：
10.1371/journal.pone.0114713
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Bertolini F
中科院分区：
文献类型：
--
作者：
Mancuso P;Calleri A;Gregato G;Labanca V;Quarna J;Antoniotti P;Cuppini L;Finocchiaro G;Eoli M;Rosti V;Bertolini F
内皮不是一个同质器官。内皮细胞的异质性已在细胞形态、功能、基因表达和抗原组成水平上描述。由于遗传、转录组和周围环境的多样性，来自不同血管床的内皮细胞具有不同的功能和表型。通过流式细胞术检测循环内皮细胞（CEC）是广泛用于癌症患者的方法，并且它们的数量、活力和动力学是对接受抗血管生成治疗的患者进行分层的有前景的工具。目前，CEC被鉴定为核结合抗原（DNA+）阳性，泛白细胞标志物CD 45阴性，CD 31和CD 146阳性。根据我们实验室最近验证的方法，我们研究了健康受试者和癌症患者外周血CEC上CD 109的表达。通过RT-PCR验证这些细胞的内皮性质是否存在两种内皮特异性转录物CDH 5（Ve-钙粘蛋白）和CLDN 5（Claudin 5）的mRNA水平。治疗前，乳腺癌患者和胶质母细胞瘤患者中CD 109 + CEC和存活的CD 109 + CEC水平显著高于健康对照组，治疗后其数量显著减少。与分选的CD 146 + CEC相比，在分选的CD 109 + CEC中观察到在发育中的内皮细胞CLEC 14 a、TMEM 204、ARHGEF 15、GPR 116中表达的内皮特异性转录物的水平更高，表明这些基因不仅在胚胎发生期间而且在成人血管生成中发挥重要作用。有趣的是，TEM 8（鉴定为Antrax毒素受体1，Antrax 1）的mRNA水平在CD 109 + CEC+中表达，但在CD 146 + CEC中不表达。综上所述，我们的结果表明，CD 109代表了一种罕见的循环肿瘤内皮细胞，在胶质母细胞瘤患者中发挥着潜在有用的预后作用。CD 109在癌血管特异性内皮细胞中的表达作用值得通过基因表达研究进一步研究。
The endothelium is not a homogeneous organ. Endothelial cell heterogeneity has been described at the level of cell morphology, function, gene expression, and antigen composition. As a consequence of the genetic, transcriptome and surrounding environment diversity, endothelial cells from different vascular beds have differentiated functions and phenotype. Detection of circulating endothelial cells (CECs) by flow cytometry is an approach widely used in cancer patients, and their number, viability and kinetic is a promising tool to stratify patient receiving anti-angiogenic treatment. Currently CECs are identified as positive for a nuclear binding antigen (DNA+), negative for the pan leukocyte marker CD45, and positive for CD31 and CD146. Following an approach recently validated in our laboratory, we investigated the expression of CD109 on CECs from the peripheral blood of healthy subject and cancer patients. The endothelial nature of these cells was validated by RT-PCR for the presence of m-RNA level of CDH5 (Ve-Cadherin) and CLDN5 (Claudin5), two endothelial specific transcripts. Before treatment, significantly higher levels of CD109+ CECs and viable CD109+CECs were found in breast cancer patients and glioblastoma patients compared to healthy controls, and their number significantly decreased after treatment. Higher levels of endothelial specific transcripts expressed in developing endothelial cells CLEC14a, TMEM204, ARHGEF15, GPR116, were observed in sorted CD109+CECs when compared to sorted CD146+CECs, suggesting that these genes can play an important role not only during embryogenesis but also in adult angiogenesis. Interestingly, mRNA levels of TEM8 (identified as Antrax Toxin Receptor1, Antrax1) were expressed in CD109+CECs+ but not in CD146+CECs. Taken together our results suggest that CD109 represent a rare population of circulating tumor endothelial cells, that play a potentially useful prognostic role in patients with glioblastoma. The role of CD109 expression in cancer vessel-specific endothelial cells deserves to be further investigated by gene expression studies.
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