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

单核细胞趋化蛋白-1治疗恶性胶质瘤新疗法的开发计划

基本信息

批准号：
09671430
负责人：
KURATSU Jun-ichi
金额：
$ 1.92万
依托单位：
Kagoshima University (1998)Kumamoto University (1997)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09671430/
关键词：
MCP-1 Glioma Angiogenesis Macrophage Macrophage グリオーママクロファージサイトカイン

项目摘要

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.

我们之前从培养的人胶质瘤细胞系的上清液中纯化了人单核细胞趋化蛋白-1（MCP-1）。 MCP-1 是调节单核细胞趋化性的 C-C 趋化因子的成员。克隆MCP-1 cDNA后，母羊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，这种趋化因子的过度表达可以诱导巨噬细胞浸润并抑制体内肿瘤生长。MCP-1 受体（称为 hCCR2）是人类免疫缺陷病毒 (HIV) 进入细胞的重要辅助受体，如，以及 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有元件、CAAT盒和TATA盒，形成单一转录起始位点。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，该酶在胶质瘤组织中发挥着重要作用。新生血管形成中发挥重要作用。我们认为巨噬细胞MCP-1活性的调节和CCR2表达的控制应导致神经胶质瘤的生长控制。