Lissoni P, Malugani F, Bonfanti A, Bucovec R, Secondino S, Brivio F, Ferrari-Bravo A, Ferrante R, Vigoré L, Rovelli F, Mandalà M, Viviani S, Fumagalli L, Gardani G S
Division of Radiation Oncology, San Gerardo Hospital, Monza, Italy.
J Biol Regul Homeost Agents. 2001 Apr-Jun;15(2):140-4.
Elevated VEGF blood concentrations have been proven to be associated with poor prognosis in human neoplasms. This finding is generally explained as a consequence of the potential angiogenic properties of VEGF itself. However, preliminary experimental studies suggest that VEGF, in addition to its angiogenic activity, may also play an immunosuppressant role by inhibiting dendritic cell (DC) maturation. The present study was performed to analyze blood levels of VEGF in cancer patients in relation to those of another potentially angiogenic tumor growth factor, endothelin-1 (ET-1), and to the absolute number of circulating immature and mature DC, and serum levels of the best known antitumor cytokine, IL-12. The study was performed in 100 healthy controls and in 80 solid tumor patients (colorectal cancer: 24; gastric cancer: 17; cancer of pancreas: 4; lung cancer: 13; breast cancer: 11; renal cell cancer: 6; gynecologic tumors: 5), 48 of whom showed distant organ metastases. In each patient, we have evaluated serum concentrations of VEGF-165, total VEGF, ET-1, IL-12 and the circulating number of immature (CD123+) and mature (CD11c+) DC. Mean serum levels of VEGF-165 were significantly higher in metastatic patients than in controls or in non-metastatic patients, whereas the total amounts of VEGF were not significantly higher. Moreover, it has been observed that patients with abnormally elevated blood concentrations of VEGF-165 showed significantly lower mean values of immature DC, mature DC and IL-12 and significantly higher mean levels of ET-1 than those with normal concentrations. This study, by confirming that advanced neoplastic disease may be associated with increased endogenous secretion of VEGF, seems to suggest that the association between high blood levels of VEGF and poor prognosis in cancer does not depend only on VEGF-induced stimulation of the neovascularization, but also on VEGF-related immunosuppression.
血液中血管内皮生长因子（VEGF）浓度升高已被证明与人类肿瘤的不良预后相关。这一发现通常被解释为VEGF本身具有潜在血管生成特性的结果。然而，初步实验研究表明，VEGF除了具有血管生成活性外，还可能通过抑制树突状细胞（DC）成熟发挥免疫抑制作用。本研究旨在分析癌症患者血液中VEGF水平与另一种潜在的血管生成性肿瘤生长因子内皮素-1（ET-1）水平、循环中未成熟和成熟DC的绝对数量以及最著名的抗肿瘤细胞因子白细胞介素-12（IL-12）血清水平之间的关系。该研究纳入了100名健康对照者和80名实体瘤患者（结直肠癌：24例；胃癌：17例；胰腺癌：4例；肺癌：13例；乳腺癌：11例；肾细胞癌：6例；妇科肿瘤：5例），其中48例有远处器官转移。在每位患者中，我们评估了血清中VEGF-165、总VEGF、ET-1、IL-12的浓度以及未成熟（CD123+）和成熟（CD11c+）DC的循环数量。转移性患者血清VEGF-165的平均水平显著高于对照组或非转移性患者，而VEGF的总量并无显著升高。此外，还观察到VEGF-165血液浓度异常升高的患者，其未成熟DC、成熟DC和IL-12的平均值显著低于正常浓度患者，而ET-1的平均水平显著高于正常浓度患者。本研究通过证实晚期肿瘤疾病可能与VEGF内源性分泌增加有关，似乎表明血液中VEGF水平高与癌症预后不良之间的关联不仅取决于VEGF诱导的新血管形成刺激，还取决于VEGF相关的免疫抑制作用。
