Fürstenberger G, von Moos R, Lucas R, Thürlimann B, Senn H-J, Hamacher J, Boneberg E-M
Center for Tumor Detection and Prevention, Rorschacherstrasse 150, 9006 St Gallen, Switzerland.
Br J Cancer. 2006 Feb 27;94(4):524-31. doi: 10.1038/sj.bjc.6602952.
Circulating endothelial cells (CECs) as well as bone-marrow-derived endothelial precursor cells (EPC) play an important role in neovascularisation and tumour growth. To study the impact of neoadjuvant chemotherapy on the amounts of CEC and their precursor cells, mature CEC and their progenitors were quantified by flow cytometry in peripheral blood of breast cancer patients during anthracycline and/or taxane based neoadjuvant chemotherapy and subsequent surgery in comparison to age-matched healthy controls. Cell numbers were tested for correlation with serum levels of angiopoietin-2, erythropoietin, endostatin, endoglin, VEGF and sVCAM-1 as well as clinical and pathological features of breast cancer disease. Circulating endothelial cells were significantly elevated in breast cancer patients and decreased during chemotherapy, whereas EPC (CD34+/VEGFR-2+) as well as their progenitor cell population CD133+/CD34+ and the population of CD34+ stem cells increased. Concomitantly with the increase of progenitor cells an increase of VEGF, erythropoietin and angiopoietin-2 was observed. These data suggest that chemotherapy can only reduce the amounts of mature CEC, probably reflecting detached cells from tumour vessels, whereas the EPC and their progenitors are mobilised by chemotherapy. Since this mobilisation of EPC may contribute to tumour neovascularisation an early antiangiogenic therapy in combination with chemotherapy could be beneficial for the success of cancer therapy.
循环内皮细胞（CECs）以及骨髓来源的内皮祖细胞（EPC）在新生血管形成和肿瘤生长中发挥着重要作用。为了研究新辅助化疗对CEC及其前体细胞数量的影响，在基于蒽环类药物和/或紫杉烷类的新辅助化疗期间及随后手术过程中，通过流式细胞术对乳腺癌患者外周血中的成熟CEC及其祖细胞进行定量，并与年龄匹配的健康对照进行比较。检测细胞数量与血管生成素-2、促红细胞生成素、内皮抑素、内皮糖蛋白、血管内皮生长因子（VEGF）和可溶性血管细胞黏附分子-1（sVCAM-1）的血清水平以及乳腺癌疾病的临床和病理特征之间的相关性。乳腺癌患者的循环内皮细胞显著升高，化疗期间减少，而EPC（CD34+/VEGFR-2+）及其祖细胞群CD133+/CD34+以及CD34+干细胞群增加。随着祖细胞数量的增加，观察到VEGF、促红细胞生成素和血管生成素-2增加。这些数据表明，化疗只能减少成熟CEC的数量，这可能反映了从肿瘤血管脱落的细胞，而EPC及其祖细胞则被化疗动员。由于EPC的这种动员可能有助于肿瘤新生血管形成，早期抗血管生成治疗联合化疗可能有利于癌症治疗的成功。
