Quantity and clinical relevance of circulating endothelial progenitor cells in human ovarian cancer.

Quantity and clinical relevance of circulating endothelial progenitor cells in human ovarian cancer.
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DOI:
10.1186/1756-9966-29-27
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发表时间:
2010-03-24
期刊:
Journal of experimental & clinical cancer research : CR
影响因子:
--
通讯作者:
Bao J
Bao J
中科院分区:
其他
文献类型:
--
作者:
Su Y;Zheng L;Wang Q;Li W;Cai Z;Xiong S;Bao J

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循环骨髓来源的内皮祖细胞(EPCs)已被报道参与肿瘤血管生成和生长,然而,循环EPCs在肿瘤进展中的作用是有争议的。循环EPCs在卵巢癌进展和血管生成中的作用尚未研究。采用流式细胞术检测25例健康志愿者和42例卵巢癌患者外周血中EPCs的数量。通过CD 34和血管内皮生长因子受体2(VEGFR 2)的共表达来定义EPCs。此外,我们通过实时逆转录聚合酶链反应测定了CD 34和VEGFR 2 mRNA水平。采用酶联免疫吸附法测定血浆血管内皮生长因子(VEGF)和基质金属蛋白酶-9(MMP-9)水平。卵巢癌患者循环中EPCs水平显著升高,与肿瘤分期和残留肿瘤大小相关。在III期和IV期卵巢癌患者中检测到的EPCs水平高于I期和II期疾病患者。肿瘤切除后,EPCs水平迅速下降。残留肿瘤大于2 cm与EPCs水平显著升高相关。此外,高循环EPCs与较差的总生存率相关。与健康对照组相比,卵巢癌患者治疗前CD 34 mRNA水平没有显著增加;然而,VEGFR 2表达增加,VEGF和MMP-9的血浆水平也升高。我们的研究结果证实了循环EPCs在卵巢癌中的临床相关性。EPCs可能是监测卵巢癌进展、血管生成和治疗反应的潜在生物标志物。
Circulating bone marrow-derived endothelial progenitor cells (EPCs) have been reported to participate in tumor angiogenesis and growth; however, the role of circulating EPCs in tumor progression is controversial. The role of circulating EPCs in ovarian cancer progression and angiogenesis has not yet been investigated. The number of circulating EPCs in the peripheral blood in 25 healthy volunteers and 42 patients with ovarian cancer was determined by flow cytometry. EPCs were defined by co-expression of CD34 and vascular endothelial growth factor receptor 2 (VEGFR2). In addition, we determined CD34 and VEGFR2 mRNA levels by real-time reverse transcription-polymerase chain reaction. Plasma levels of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) were determined by enzyme-linked immunosorbent assay. Circulating levels of EPCs were significantly increased in ovarian cancer patients, correlating with tumor stage and residual tumor size. Higher levels of EPCs were detected in patients with stage III and IV ovarian cancer than in patients with stage I and II disease. After excision of the tumor, EPCs levels rapidly declined. Residual tumor size greater than 2 cm was associated with significantly higher levels of EPCs. In addition, high circulating EPCs correlated with poor overall survival. Pretreatment CD34 mRNA levels were not significantly increased in ovarian cancer patients compared with healthy controls; however, VEGFR2 expression was increased, and plasma levels of VEGF and MMP-9 were also elevated. Our results demonstrate the clinical relevance of circulating EPCs in ovarian cancer. EPCs may be a potential biomarker to monitor ovarian cancer progression and angiogenesis and treatment response.