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

我们先前从人脑胶质瘤细胞系培养上清液中纯化了人单核细胞趋化蛋白-1(MCP-1)。单核细胞趋化蛋白-1是C-C趋化因子中的一员，主要作用于单核细胞的趋化。克隆MCP-1基因后，我们对该基因在多种脑肿瘤中的表达进行了分析。发现肿瘤组织中MCP-1的表达与肿瘤相关巨噬细胞数量呈正相关。MCP-1受体，命名为hCCR2，是人类免疫缺陷病毒(HIV)进入细胞所必需的辅助受体，也是MCP-1的受体。为了阐明hCCR2转录调控的分子机制，我们对hCCR2基因进行了克隆和测序。在5-侧翼区域，存在典型的哺乳动物启动子共同元件，即CAAT盒和TATA盒，导致了单一的转录起始点。此外，我们还发现，渗透到胶质瘤组织中的显微图像表达了在新生血管中起重要作用的酪氨酸磷酸化酶。我们认为单核细胞趋化蛋白-1活性的调节和巨噬细胞CCR2表达的调控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.