Circulating endothelial cells and angiogenic serum factors during neoadjuvant chemotherapy of primary breast cancer.

Circulating endothelial cells and angiogenic serum factors during neoadjuvant chemotherapy of primary breast cancer.
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DOI:
10.1038/sj.bjc.6602952
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发表时间:
2006-02-27
影响因子:
8.8
通讯作者:
--
中科院分区:
医学1区
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--
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循环内皮细胞(CEC)以及骨髓源性内皮前体细胞(EPC)在新血管形成和肿瘤生长中发挥重要作用。为了研究新辅助化疗对 CEC 及其前体细胞数量的影响,与年龄匹配的健康对照相比,在基于蒽环类和/或紫杉烷的新辅助化疗和随后的手术期间,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。测试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、VEGF和sVCAM-1的血清水平以及乳腺癌疾病的临床和病理特征的相关性。乳腺癌患者的循环内皮细胞显着升高,化疗期间减少,而 EPC (CD34+/VEGFR-2+) 及其祖细胞群 CD133+/CD34+ 和 CD34+ 干细胞群增加。随着祖细胞的增加,观察到VEGF、促红细胞生成素和血管生成素-2也增加。这些数据表明化疗只能减少成熟 CEC 的数量,这可能反映了细胞与肿瘤血管的分离,而 EPC 及其祖细胞则通过化疗被动员起来。由于 EPC 的动员可能有助于肿瘤新生血管形成,因此早期抗血管生成治疗与化疗相结合可能有利于癌症治疗的成功。
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.
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