Tas Faruk, Duranyildiz Derya, Oguz Hilal, Camlica Hakan, Yasasever Vildan, Topuz Erkan
Institute of Oncology, Istanbul University, Capa, Istanbul, Turkey.
Melanoma Res. 2006 Oct;16(5):405-11. doi: 10.1097/01.cmr.0000222598.27438.82.
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-beta1 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-beta1 (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-beta1, 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-beta1 (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-beta1 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.
血管生成对于肿瘤进展和转移至关重要；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，我们分析了人类黑色素瘤患者循环血清中强效血管生成因子的水平，包括血管内皮生长因子（VEGF）、血管生成素、转化生长因子-β1以及VEGF受体VEGFR1和VEGFR2。研究了114例不同阶段经组织病理学证实的皮肤黑色素瘤患者和30名健康对照者。通过固相酶联免疫吸附测定法定量分析血管生成因子和VEGF受体的血清水平。患者年龄（61名男性和53名女性）在18至80岁之间；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）、VEGF（P = 0.006）和VEGFR1（P = 0.007）水平显著高于对照组。然而，黑色素瘤患者与对照组之间血清血管生成素和VEGFR2水平无显著差异。发现血清转化生长因子-β1、VEGF和VEGFR1水平升高与疾病晚期呈正相关。仅在VEGF和VEGFR2血清水平之间发现显著关系。发现血清转化生长因子-β1水平升高（P < 0.001）和VEGF水平升高（P = 0.0012）是不良预后因素。然而，血管生成素和VEGF受体的血清水平对生存率没有影响。我们的数据表明，黑色素瘤患者中包括VEGF、转化生长因子-β1和VEGFR1在内的血管生成血清因子升高，尤其是与疾病晚期相关。VEGF调节血管生成的机制可能部分归因于VEGFRs，尤其是VEGFR1的增殖增强。
