a Department of Medical Biotechnology and Translational Medicine , LITA-Segrate, University of Milan , Milan , Italy.
b Laboratory of Experimental Neurosurgery and Cell Therapy, Neurosurgery Unit, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico , University of Milan , Milan , Italy.
Platelets. 2017 Sep;28(6):585-594. doi: 10.1080/09537104.2016.1247208. Epub 2016 Nov 29.
Glioblastoma multiforme (GBM) is the most common and fatal intracranial cancer in humans and exhibits intense and aberrant angiogenesis that sustains its malignancy and involves several angiogenic signals. Among them, vascular endothelial growth factor (VEGF) plays a key role and is overexpressed in GBM. Different cells appear to act as triggers of the aberrant angiogenesis, and, among them, platelets act as key participants. In order to provide further insights into the platelet features and angiogenic role in GBM, this study investigated the effects of platelet releasate on GBM-derived endothelial cells (GECs) and the levels of VEGF and endostatin, as pro- and anti-angiogenic components of platelet releasate from GBM patients. We demonstrate for the first time that: 1) platelet releasate exerts powerful pro-angiogenic effect on GECs, suggesting it might exert a role in the aberrant angiogenesis of GBM; 2) ADP and thrombin stimulation leads to significantly higher level of VEGF, but not of endostatin, in the releasate of platelets from GBM patients than those from healthy subjects; and 3) the intraplatelet concentrations of VEGF were significantly elevated in GBM patients as compared to controls. Moreover, we found a direct correlation between platelet-released VEGF and overall survival in our patient cohort. Although preliminary, these findings prompt further investigations to clarify the biologic relevance of platelet VEGF in GBM and prospective studies for screening GBM patients for anti-VEGF therapy and/or to optimize this treatment.
胶质母细胞瘤（GBM）是人类最常见和致命的颅内癌症，表现出强烈和异常的血管生成，维持其恶性程度，并涉及几种血管生成信号。其中，血管内皮生长因子（VEGF）起着关键作用，并在 GBM 中过度表达。不同的细胞似乎作为异常血管生成的触发因素起作用，其中血小板作为关键参与者。为了进一步深入了解血小板在 GBM 中的特征和血管生成作用，本研究调查了血小板释放物对 GBM 衍生的内皮细胞（GEC）以及 VEGF 和内皮抑素水平的影响，VEGF 和内皮抑素是 GBM 患者血小板释放物中的促血管生成和抗血管生成成分。我们首次证明：1）血小板释放物对 GEC 具有强大的促血管生成作用，表明其可能在 GBM 的异常血管生成中发挥作用；2）ADP 和凝血酶刺激导致 GBM 患者血小板释放物中的 VEGF 水平明显高于健康受试者，但内皮抑素水平没有增加；3）与对照组相比，GBM 患者的血小板内 VEGF 浓度明显升高。此外，我们在患者队列中发现血小板释放的 VEGF 与总生存期之间存在直接相关性。尽管这些发现是初步的，但它们促使进一步研究以阐明血小板 VEGF 在 GBM 中的生物学相关性，并进行前瞻性研究以筛选 GBM 患者接受抗 VEGF 治疗和/或优化这种治疗。
