Gunsilius E, Petzer A, Stockhammer G, Nussbaumer W, Schumacher P, Clausen J, Gastl G
Division of Hematology and Oncology, University Hospital, Innsbruck, Austria.
Oncology. 2000 Feb;58(2):169-74. doi: 10.1159/000012095.
Serum levels of vascular endothelial growth factor (VEGF-S) have been reported to correlate with tumor stage and prognosis in various human malignancies. The source of soluble VEGF in peripheral blood remains obscure. We therefore measured the concentration of immunoreactive VEGF in 241 serum samples and 61 plasma samples (VEGF-P) from 20 subjects undergoing myeloablative chemotherapy and from 3 normal platelet donors. A significant correlation between the peripheral blood platelet count (PC) and VEGF-S (r = 0.86) but not VEGF-P was found. VEGF-S levels were 58.43 +/- 42.50 pg/ml (mean +/- SD) in patients with a PC < 50 x 10(9)/l, 203.29 +/- 176.56 pg/ml for a PC of 50-150 x 10(9)/l, and 457.42 +/- 475.41 pg/ml for a PC > 150 x 10(9)/l. Interestingly, VEGF-P levels were substantially lower than the corresponding VEGF-S values, namely below the detection limit in most cases. Supernatants from platelet-rich plasma contained no VEGF, but after in vitro lysis of the platelets very high VEGF levels were found. The VEGF content per 10(9) platelets was calculated at 2.51 +/- 2.39 pg and was dependent on the mean platelet volume. In summary, VEGF release from platelets during blood clotting was found to be the main source of VEGF in serum samples. Cancer patients in clinical remission have negligible amounts of soluble VEGF in peripheral blood, and myeloablative chemotherapy causes a significant drop in VEGF-S levels corresponding to the decrease in PC. Thus, studies addressing the diagnostic and prognostic value of VEGF-S in cancer patients must be interpreted with caution. Our data provide the basis for predicting VEGF-S in relation to PC in vivo, and for reevaluating former studies of VEGF-S in patients with malignant or nonmalignant disease.
据报道，血管内皮生长因子（VEGF-S）的血清水平与多种人类恶性肿瘤的肿瘤分期和预后相关。外周血中可溶性VEGF的来源仍不清楚。因此，我们检测了20例接受清髓性化疗的患者以及3名正常血小板供者的241份血清样本和61份血浆样本（VEGF-P）中免疫反应性VEGF的浓度。结果发现外周血血小板计数（PC）与VEGF-S之间存在显著相关性（r = 0.86），而与VEGF-P无相关性。PC < 50×10⁹/l的患者VEGF-S水平为58.43±42.50 pg/ml（平均值±标准差），PC为50 - 150×10⁹/l时为203.29±176.56 pg/ml，PC > 150×10⁹/l时为457.42±475.41 pg/ml。有趣的是，VEGF-P水平显著低于相应的VEGF-S值，在大多数情况下低于检测限。富含血小板血浆的上清液中不含VEGF，但血小板体外裂解后发现VEGF水平非常高。每10⁹个血小板的VEGF含量经计算为2.51±2.39 pg，且依赖于平均血小板体积。总之，发现血液凝固过程中血小板释放的VEGF是血清样本中VEGF的主要来源。临床缓解期的癌症患者外周血中可溶性VEGF含量可忽略不计，清髓性化疗导致VEGF-S水平显著下降，与PC的降低相对应。因此，关于VEGF-S在癌症患者中的诊断和预后价值的研究必须谨慎解读。我们的数据为体内预测与PC相关的VEGF-S以及重新评估既往关于恶性或非恶性疾病患者VEGF-S的研究提供了依据。
