HUMAN ASTROCYTOMAS AND GLIOBLASTOMAS EXPRESS MONOCYTE CHEMOATTRACTANT PROTEIN-1 (MCP-1) IN-VIVO AND IN-VITRO

HUMAN ASTROCYTOMAS AND GLIOBLASTOMAS EXPRESS MONOCYTE CHEMOATTRACTANT PROTEIN-1 (MCP-1) IN-VIVO AND IN-VITRO
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DOI:
10.1002/ijc.2910580216
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发表时间:
1994-07-15
影响因子:
6.4
通讯作者:
VAN MEIR, EG
VAN MEIR, EG
中科院分区:
医学1区
文献类型:
--
作者:
DESBAILLETS, I;TADA, M;VAN MEIR, EG

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单核细胞趋化蛋白-1(MCP-1)的表达在人类中枢神经系统肿瘤(胶质母细胞瘤和星形细胞瘤)和正常人脑中进行了检查。北方印迹分析显示12个胶质母细胞瘤细胞系中有6个细胞系表达MCP-1 mRNA。在所有测试的细胞系中,白细胞介素(IL)-1 β和肿瘤坏死因子(TNF)-α均可刺激表达。免疫沉淀证实了MCP-1蛋白的两种亚型MCP-1 α和MCP-1 β的分泌。逆转录聚合酶链反应和北方印迹分析显示MCP-1 mRNA在17例胶质母细胞瘤、6例间变性星形细胞瘤和6例低级别星形细胞瘤中均有表达,在胎儿脑中也有表达,而在正常成人脑中无表达。2例胶质母细胞瘤和1例低级别星形细胞瘤的原位杂交结果表明,肿瘤性星形细胞和内皮细胞表达MCP-1 mRNA。此外,在体外试验中,胶质母细胞瘤和星形细胞瘤的肿瘤囊液能够诱导单核细胞化学吸引。在10个样品中的9个中,这种趋化活性被抗MCP-1抗体特异性中和,进一步证明了生物活性MCP-1在体内的产生,并支持该因子在单核细胞/巨噬细胞浸润到肿瘤组织中的重要作用。(C)1994 Wiley-Liss,Inc.
Expression of the monocyte chemoattractant protein-1 (MCP-1) was examined in human central nervous system tumours (glioblastomas and astrocytomas) and normal human brain. Northern blot analysis demonstrated constitutive expression of MCP-1 mRNA in 6 of 12 glioblastoma cell lines. Expression could be stimulated by interleukin (IL)-1 beta and tumour necrosis factor (TNF)-alpha in all cell lines tested. Immunoprecipitation demonstrated secretion of both isoforms, MCP-1 alpha and -beta, of the MCP-1 protein. Reverse-transcription polymerase chain reaction and Northern blot analysis on tissues demonstrated MCP-1 mRNA expression in 17 of 17 glioblastomas, 3 of 6 anaplastic astrocytomas and 6 of 6 low-grade astrocytomas, as well as in fetal brain but not in normal adult brain. In situ hybridization on 2 glioblastomas and 1 low-grade astrocytoma indicates that neoplastic astrocytes and endothelial cells express MCP-1 mRNA in vivo. Moreover, tumour cyst fluids of glioblastomas and astrocytomas were able to induce monocyte chemoattraction in an in vitro assay. This chemotactic activity was specifically neutralized by anti-MCP-1 antibodies in 9 of 10 samples, further demonstrating the production of bioactive MCP-1 in vivo and supporting an important role for this factor in the infiltration of monocytes/macrophages into tumour tissue. (C) 1994 Wiley-Liss, Inc.