Glioblastoma-associated circulating monocytes and the release of epidermal growth factor
Glioblastoma-associated circulating monocytes and the release of epidermal growth factor
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DOI：
10.3171/jns.1996.85.4.0642
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发表时间：
1996-10-01
影响因子：
4.1
通讯作者：
Kempski, O
中科院分区：
文献类型：
--
作者：
Fries, G;Perneczky, A;Kempski, O
单核细胞/巨噬细胞经常浸润恶性胶质瘤，并在肿瘤相关免疫应答中发挥核心作用，因为它们处理肿瘤抗原并将其呈递给T淋巴细胞。研究发现，离开脑循环的外周血单核细胞变成小胶质细胞，反之亦然，单核细胞/巨噬细胞可能通过某种未知机制刺激恶性肿瘤生长。大多数恶性神经胶质瘤表达生长因子受体，例如表皮生长因子受体（EGFR）。本研究的目的是确定胶质瘤患者外周血单核细胞是否释放EGF，胶质细胞膜结合EGFR的适当配体。使用EGF的酶联免疫吸附测定法，在培养的第7天、第21天和第100天测定细胞培养上清液的EGF含量。EGF含量在培养的第7天，上清液的浓度（平均值+/-标准误差）为5.9 +/-0.2 pg/ml/10（3）胶质瘤单核细胞对1.3 +/-0.1 pg/ml/10（3）对照单核细胞，22.9 +/- 0.8 pg/ml/10（3）胶质瘤单核细胞与1.8 +/- 0.9 pg/ml/10（3）对照单核细胞在培养第21天，和23.4 +/- 0.7 pg/ml/10（3）胶质瘤单核细胞，并且在培养的第100天低于对照单核细胞的检测水平。胶质瘤患者的类固醇治疗不影响培养的单核细胞的EGF释放。这些数据表明，胶质母细胞瘤相关的外周血单核细胞可能不同于健康个体。此外，这项研究表明，胶质瘤相关的外周血单核细胞亚型可能支持免疫抑制，并通过释放异常高的EGF促进恶性胶质瘤的生长。
Monocytes/macrophages frequently infiltrate malignant gliomas and play a central role in the tumor-associated immune response as they process tumor antigen and present it to T-lymphocytes. Findings have accumulated that peripheral blood monocytes leaving the cerebral circulation become microglial cells and vice versa and that monocytes/macrophages may stimulate malignant tumor growth by some unknown mechanism. Most malignant gliomas express growth factor receptors, for example epidermal growth factor receptor (EGFR). The aim of this study was to determine whether peripheral blood monocytes of glioma patients release EGF, the appropriate ligand of gliomncell membrane-bound EGFR.Long-term cultured peripheral blood monocytes from 14 patients with malignant gliomas were compared to those from 12 controls (seven with nontumorous disease and five healthy individuals). Using an enzyme-linked immunosorbent assay for EGF, the EGF content of cell culture supernatants was determined at Days 7, 21, and 100 of culture. The EGF content (mean +/- standard error) of supernatants was 5.9 +/- 0.2 pg/ml/10(3) glioma monocytes versus 1.3 +/- 0.1 pg/ml/10(3) control monocytes at Day 7 of culture, 22.9 +/- 0.8 pg/ml/10(3) glioma monocytes versus 1.8 +/- 0.9 pg/ml/10(3) control monocytes at Day 21 of culture, and 23.4 +/- 0.7 pg/ml/10(3) glioma monocytes, and below detection levels for control monocytes at Day 100 of culture. Steroid treatment of glioma patients did not influence the EGF release of cultured monocytes. These data indicate that glioblastoma-associated peripheral blood monocytes may be distinct from those of healthy individuals. Moreover, this study indicates that subtypes of glioma-associated peripheral blood monocytes may support immunosuppression and promote growth of malignant glioma by releasing unusually high amounts of EGF.