Circulating serum levels of angiogenic factors and vascular endothelial growth factor receptors 1 and 2 in melanoma patients

Circulating serum levels of angiogenic factors and vascular endothelial growth factor receptors 1 and 2 in melanoma patients
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DOI:
10.1097/01.cmr.0000222598.27438.82
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发表时间:
2006-10-01
期刊:
影响因子:
2.2
通讯作者:
Topuz, Erkan
Topuz, Erkan
中科院分区:
医学4区
文献类型:
--
作者:
Tas, Faruk;Duranyildiz, Derya;Topuz, Erkan

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血管生成对于肿瘤的进展和转移是必不可少的;然而,与黑色素瘤生物学相关的血管生成调节因子仍然未知。在本研究中,我们分析了黑色素瘤患者循环血清中强大的血管生成因子水平,包括血管内皮生长因子(VEGF)、血管生成素、转化生长因子-β1及其受体VEGFR1和VEGFR2。对114例经组织病理学证实的不同时期皮肤黑色素瘤患者和30例健康对照进行了研究。采用固相酶联免疫吸附试验定量检测血清血管生成因子和血管内皮生长因子受体水平。这些患者(61名男性和53名女性)的年龄从18岁到80岁不等;中位年龄为51岁。黑色素瘤患者血清转化生长因子-β1(P<0.001)、血管内皮生长因子(P=0.006)和血管内皮生长因子受体1(P=0.007)水平显著高于对照组。然而,在黑色素瘤患者和对照组之间,血清血管生成素和VEGFR2水平没有显著差异。血清转化生长因子-β1、血管内皮生长因子和血管内皮生长因子受体水平的升高与疾病的进展呈正相关。只有血清中的血管内皮生长因子和血管内皮细胞生长因子R2之间存在显著的相关性。血清转化生长因子-β1(P<0.001)和血管内皮生长因子水平升高(P=0.0012)是预后不良的因素。然而,血清血管生成素和血管内皮生长因子受体水平对存活率没有影响。我们的数据提示,在黑色素瘤患者中,血管生成因子,包括血管生成因子,包括转化生长因子-β1和VEGFR1,而不是血管生成素和VEGFR2,在黑色素瘤患者中升高,特别是与疾病晚期相关。血管内皮生长因子调节血管生成的机制可能部分是由于促进了血管内皮生长因子受体,尤其是血管生长因子受体1的增殖。
Angiogenesis is essential for tumor progression and metastasis; however, the angiogenesis regulators that are biologically relevant for melanoma are still unknown. In this study, we analyzed the circulating serum levels of potent angiogenic factors, including vascular endothelial growth factor (VEGF), angiogenin, transforming growth factor-beta 1 and VEGF receptors, VEGFR1 and VEGFR2, in human melanoma patients. One hundred and fourteen patients with histopathologically verified cutaneous melanoma at different stages and 30 healthy controls were investigated. Serum levels of angiogenic factors and VEGF receptors were quantitatively analyzed by solid-phase enzyme-linked immunosorbent assay. The age of the patients (61 men and 53 women) ranged from 18 to 80 years; median age was 51 years. Serum transforming growth factor-beta 1 (P < 0.001), VEGF (P=0.006) and VEGFR1 (P=0.007) levels were significantly higher in patients with melanoma than in the control group. No significant differences, however, exist in the serum angiogenin and VEGFR2 levels between melanoma patients and the controls. The positive correlations of elevated serum levels of transforming growth factor-beta 1, VEGF and VEGFR1 with advanced stages of disease were found. Significant relationship was found only between serum levels of VEGF and VEGFR2. Elevated serum transforming growth factor-beta 1 (P < 0.001) and VEGF levels (P=0.0012) were found to be poor prognostic factors. Serum level of angiogenin and VEGF receptors, however, had no effect on survival. Our data suggest that the angiogenic serum factors, including VEGF, transforming growth factor-beta 1 and VEGFR1, but not angiogenin and VEGFR2 were increased in melanoma patients, especially associated with advanced disease stages. The mechanism of VEGF regulation of angiogenesis may in part be due to enhanced proliferation of VEGFRs, especially VEGFR1.