Development plan of the new treatment for malignant glioma using Monocyte Chemoattrctant Protein-1

我们以前纯化的人单核细胞趋化蛋白-1（MCP-1）培养的人脑胶质瘤细胞系的上清液。MCP-1是C-C趋化因子的成员，其抑制单核细胞趋化性。克隆MCP-1 cDNA后，我们分析了该基因在多种脑肿瘤中的表达。发现肿瘤组织中MCP-1的表达量与肿瘤相关巨噬细胞的数量呈正相关。此外，转染实验表明，该趋化因子的过度表达可以诱导巨噬细胞浸润和抑制体内肿瘤生长。MCP-1受体，命名为hCCR 2，是人类免疫缺陷病毒（HIV）进入细胞的必需辅助受体，也是MCP-1的受体。为了阐明hCCR 2转录调控的分子机制，我们克隆了hCCR 2基因并进行了序列测定。在5-侧翼区有典型的哺乳动物启动子共有元件，一个CAAT盒和一个TATA盒，形成一个转录起始位点。此外，我们还发现浸润到胶质瘤组织中的巨噬细胞表达酪氨酸磷酸化酶，该酶在胶质瘤新生血管形成中起重要作用。我们认为调节巨噬细胞的MCP-1活性和控制CCR 2的表达可能导致胶质瘤的生长控制。

We previously purified the human monocyte chemoattractant protein-1(MCP-1) from supernatant of cultured human glioma cell lines. MCP-1 is a member of the C-C chemokines that medicate monocyte chemotaxis. After cloning of the MCP-1 cDNA, ewe hacve analyzed the expression of the gene In a variety of brain tumors. We found the therewas a positive correatlon between the amount of MCP-1 expression of the tumors and the number of tumor associated macrophages. Furthermore, a transfection experiment demonstrated that excessive expression of this chemokine could induce macrophage infiltration and suppression In vivo tumor growth.The MCP-1 receptor, designated hCCR2, is an essential co-receptor In cell entry by the human immunodeficiency virus (HIV) as , well as a receptor for MCP-1. To elucidate the molecular mechanisms for transcriptional regulation of hCCR2, we cloned and sequenced the hCCR2 gene. In the 5-flanking region, there were the typical mammalian promotor consensus elements, a CAAT box and a TATA box resulting in a single transcription-Initiation site.Furthermore, we found that macraphages infiltrated into the glioma tissue express the tyrosine phosphorylase which play an important role on the neovascularization. We posit the regulation of MCP-1 activity and the control of the CCR2 expression of macrophages should lead to the growth control of glioma.