文章:
多面循环内皮细胞在癌症中的作用:迈向标志物和靶标鉴定
The multifaceted circulating endothelial cell in cancer: towards marker and target identification
原文发布日期:2006-10-05
DOI: 10.1038/nrc1971
类型: Review Article
开放获取: 否
要点:
- Circulating endothelial cells (CECs) with a mature phenotype, which are probably derived from blood vessel wall turnover, are increased in patients with some types of cancer and in various other conditions including mechanical, inflammatory, infective, ischaemic and autoimmune states.
- A subpopulation of CECs shows a progenitor-like phenotype. Preclinical and clinical data indicate that these circulating endothelial progenitors (CEPs) can incorporate in cancer vessels, albeit usually at low frequencies. Some preclinical studies suggest that CEPs have a key role in promoting cancer vasculogenesis and in late stages of cancer development. Therefore, CEP-targeting drugs (including many anti-angiogenic agents) might, in principle, inhibit cancer growth.
- CEC and CEP numbers, kinetics and viability can be measured by different approaches, including positive enrichment by immunobeads and flow cytometry. However, so far no single antigen has been successfully exploited to discriminate between endothelial and haematopoietic cells; consequently, a multiparametric investigation at the single-cell level is mandatory at present.
- CEC measurement has been found to correlate well with well-known preclinical assays of angiogenesis, such as the corneal micropocket assay, which cannot be adapted for use in patients. In addition, CEC kinetics and viability have been found to correlate with clinical outcomes in cancer patients treated with anti-angiogenic therapeutic approaches.
- CECs and/or CEPs might, in the future, be used to deliver drugs to cancer vessels.
要点翻译:
- 具有成熟表型的循环内皮细胞很可能源于血管壁的更新代谢,在特定癌症患者以及机械性、炎症性、感染性、缺血性和自身免疫性疾病等多种其他病理状态下会增多。
- 循环内皮细胞的一个亚群表现出祖细胞样表型。临床前和临床数据表明,这些循环内皮祖细胞能够掺入肿瘤血管,尽管频率通常较低。部分临床前研究表明,循环内皮祖细胞在促进肿瘤血管生成及癌症晚期进展中起关键作用。因此,靶向循环内皮祖细胞的药物(包括多种抗血管生成剂)理论上可能抑制肿瘤生长。
- 目前可通过多种方法检测循环内皮细胞和循环内皮祖细胞的数量、动力学特征及活性,包括免疫磁珠阳性富集法和流式细胞术。然而迄今尚未发现单一抗原可成功区分内皮细胞与造血细胞,因此现阶段必须在单细胞水平进行多参数分析。
- 研究发现循环内皮细胞的测量结果与角膜微囊实验等公认的血管生成临床前检测方法具有良好相关性,而此类传统方法无法适用于人体研究。此外,循环内皮细胞的动力学特征和活性与接受抗血管生成治疗的癌症患者的临床结局相关。
- 未来循环内皮细胞和/或循环内皮祖细胞或可作为药物递送载体靶向肿瘤血管。
英文摘要:
Increases in the number of circulating endothelial cells (CECs) and progenitors (CEPs) have been reported in various pathological conditions including cancer. Preclinical studies have shown that CEC and CEP kinetics correlate well with several standard laboratory angiogenesis assays, which cannot be used in humans. At the clinical level, evidence is emerging that CEC kinetics and viability might correlate with clinical outcomes in cancer patients who undergo anti-angiogenic treatment. Therefore, CEC and CEP measurement has potential as a surrogate marker for monitoring anti-angiogenic treatment and drug activity, and could help to determine the optimal biological dose of anti-angiogenic drugs, which are being used with increasing frequency in medical oncology.
摘要翻译:
循环内皮细胞(CECs)及其前体细胞(CEPs)数量的增加已在包括癌症在内的多种病理状态中被报道。临床前研究表明,CEC与CEP的动力学与多项标准实验室血管生成检测高度相关,而这些检测无法在人体中进行。在临床层面,越来越多的证据显示,CEC的动力学和活性可能与接受抗血管生成治疗的癌症患者的临床结局相关。因此,CEC与CEP的检测有潜力成为监测抗血管生成治疗及药物活性的替代标志物,并有助于确定抗血管生成药物的最佳生物剂量——这类药物在肿瘤内科中的应用正日益频繁。
原文链接:
The multifaceted circulating endothelial cell in cancer: towards marker and target identification