High VEGFR-3-positive Circulating Lymphatic/Vascular Endothelial Progenitor Cell Level Is Associated with Poor Prognosis in Human Small Cell Lung Cancer
High VEGFR-3-positive Circulating Lymphatic/Vascular Endothelial Progenitor Cell Level Is Associated with Poor Prognosis in Human Small Cell Lung Cancer
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DOI：
10.1158/1078-0432.ccr-08-1372
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发表时间：
2009-03-01
影响因子：
11.5
通讯作者：
Dome, Balazs
中科院分区：
文献类型：
--
作者：
Bogos, Krisztina;Renyi-Vamos, Ferenc;Dome, Balazs
目的：新发现的骨髓来源的细胞群，称为淋巴/血管内皮祖细胞（LVEPC），已被证明有助于实验肿瘤系统中的淋巴毛细血管生长。这些细胞的临床意义尚未在人类恶性肿瘤中进行研究。我们的目的是研究外周血循环LVEPCs是否参与人小细胞肺癌（SCLC）的进展。实验设计：共88例局限期SCLC患者和32例无肿瘤对照者被包括在内。采用流式细胞术和ELISA法分别检测CD 34和VEGFR 3抗体标记的外周血循环LVEPC和血清中关键淋巴管生成分子VEGF-C的水平LVEPC计数与淋巴结转移有显著相关性（P <0.01）。高的治疗前循环LVEPC数量与低的总生存率相关（P < 0.01）。虽然我们观察到患者VEGF-C浓度显著升高（与对照组相比; P < 0.01），但VEGF-C与LVEPC水平之间无显著相关性。此外，外周血VEGF-C水平无显着差异，被视为亚组患者的临床病理变量，包括肿瘤和淋巴结分期和survival.Conclusions：外周血水平的骨髓来源的LVEPCs显着增加，小细胞肺癌患者淋巴受累和预后。这是第一项研究表明恶性肿瘤患者循环LVEPC数量增加的证据。
Purpose: The newly identified bone marrow-derived cell population, called lymphatic/vascular endothelial progenitor cells (LVEPC), has been shown to contribute to lymph capillary growth in experimental tumor systems. The clinical significance of these cells has not yet been investigated in a human malignancy. Our aim was to study whether peripheral blood circulating LVEPCs participate in the progression of human small cell lung cancer (SCLC).Experimental Design: A total of 88 patients with limited-stage SCLC and 32 tumor-free control subjects were included. Peripheral blood circulating LVEPC labeled with CD34 and vascular endothelial growth factor receptor-3 (VEGFR3) antibodies and the serum levels of the key lymphangiogenic molecule VEGF-C were measured by flow cytometry and ELISA, respectively.Results: CD34-positive/VEGFR3-positive LVEPC levels were significantly increased in patients (versus controls; P < 0.01), and there was also a significant relationship between LVEPC counts and lymph node metastasis (P < 0.01). High pretreatment circulating LVEPC numbers correlated with poor overall survival (P < 0.01). Although we observed significantly elevated VEGF-C concentrations in patients (versus controls; P < 0.01), there was no significant correlation between VEGF-C and LVEPC levels. Moreover, no significant differences in peripheral blood VEGF-C levels were seen between patients subgrouped by clinicopathologic variables including tumor and lymph node stages and survival.Conclusions: Peripheral blood levels of bone marrow-derived LVEPCs are significantly increased in patients with SCLC and correlate with lymphatic involvement and prognosis. This is the first study that shows evidence of increased numbers of circulating LVEPC in patients with a malignant tumor.