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

我们先前从培养的人胶质瘤细胞系上清中纯化了人单核细胞化学引诱蛋白-1（MCP-1）。MCP-1是单核细胞趋化作用的C-C趋化因子中的一员。在克隆MCP-1 cDNA后，我们分析了该基因在多种脑肿瘤中的表达。我们发现肿瘤中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，过度表达该趋化因子可诱导巨噬细胞浸润，抑制体内肿瘤生长。MCP-1受体，被命名为hCCR2，是人类免疫缺陷病毒（HIV）进入细胞时必不可少的辅助受体，也是MCP-1的受体。为了阐明hCCR2转录调控的分子机制，我们克隆并测序了hCCR2基因。在5侧区域，存在典型的哺乳动物启动子共识元件，CAAT盒和TATA盒导致单一转录起始位点。此外，我们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，酪氨酸磷酸化酶在新生血管中起重要作用。我们推测巨噬细胞MCP-1活性的调节和CCR2表达的控制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.