Identification and clinical significance of circulating endothelial progenitor cells in human non-small cell lung cancer
Identification and clinical significance of circulating endothelial progenitor cells in human non-small cell lung cancer
复制标题
DOI：
10.1158/0008-5472.can-05-4654
复制
发表时间：
2006-07-15
期刊：
影响因子：
11.2
通讯作者：
Tovari, Jozsef
中科院分区：
文献类型：
--
作者：
Dome, Balazs;Timar, Jozsef;Tovari, Jozsef
直到最近，人们普遍认为肿瘤的血管化完全来自于内皮细胞的发芽。循环骨髓源性内皮祖细胞（EPC）是否参与非小细胞肺癌（NSCLC）的进展尚未得到评估。用流式细胞术对53例非小细胞肺癌患者外周血中CD34、CD133和血管内皮生长因子受体-2 （VEGFR2）抗体标记的EPCs进行计数。此外，通过定量逆转录- pcr方法，我们测量了同一患者人群外周血样本中的VEGFR2、CD133、CD34和VE-cadherin mRNA。用CD31、CD34共聚焦显微镜对肿瘤样品中的EPCs进行鉴定。CD133和VEGFR2抗体。尽管微血管的免疫荧光标记表明EPCs掺入在NSCLC组织中是一种罕见的现象（22例中有9例），但治疗干预前NSCLC患者的循环EPC水平升高（P < 0.002，与健康对照组相比），预处理前高的循环EPC数量与较差的总生存率相关（P < 0.001）。此外，在治疗有反应的亚组中，治疗后外周血EPC数明显低于无反应的患者。有趣的是，在NSCLC患者中，CD133、VE-cadherin和CD34的预处理mRNA水平没有显著升高，而VEGFR2的表达增加了80倍。此外，治疗后无反应患者亚组外周血VEGFR2 mRNA水平显著高于抗肿瘤治疗后反应患者亚组。在非小细胞肺癌患者中，骨髓来源的内皮祖细胞的循环水平显著升高，并与临床行为相关。
Until recently, it was generally accepted that vascularization of tumors arises exclusively from endothelial sprouting. Whether circulating bone marrow-derived endothelial progenitor cells (EPC) participate in the progression of non-small cell lung cancer (NSCLC) has not yet been evaluated. EPCs labeled with CD34, CD133, and vascular endothelial growth factor receptor-2 (VEGFR2) antibodies were counted by flow cytometry in the peripheral blood of 53 NSCLC patients. Furthermore, by means of a quantitative reverse transcription-PCR approach, we measured VEGFR2, CD133, CD34, and VE-cadherin mRNA in the peripheral blood samples of the same patient population. EPCs in tumor samples were identified by confocal microscopy using CD31, CD34. CD133, and VEGFR2 antibodies. Although immunofluorescent labeling of microvessels made clear that incorporation of EPCs is a rare phenomenon in NSCLC tissue (9 of 22 cases), circulating EPC levels before therapeutic intervention were increased in NSCLC patients (P < 0.002, versus healthy controls), and high pretreatment circulating EPC numbers correlated with poor overall survival (P < 0.001). Furthermore, in the subgroup of responders to treatment, the posttreatment EPC numbers in the peripheral blood were significantly lower compared with nonresponding patients. Interestingly, pretreatment mRNA levels of CD133, VE-cadherin, and CD34 were not significantly increased in NSCLC patients, whereas VEGFR2 expression was increased by 80-fold. Moreover, posttreatment VEGFR2 mRNA level in the peripheral blood was significantly higher in the subgroup of nonresponding patients when compared with posttreatment level of patients responding to antitumor therapy. Circulating levels of bone marrow-derived EPCs are significantly increased in NSCLC patients and correlate with clinical behavior.