EXPRESSION OF THE JE/MCP-1 GENE SUPPRESSES METASTATIC POTENTIAL IN MURINE COLON-CARCINOMA CELLS
EXPRESSION OF THE JE/MCP-1 GENE SUPPRESSES METASTATIC POTENTIAL IN MURINE COLON-CARCINOMA CELLS
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DOI：
10.1007/bf01525986
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发表时间：
1994-10-01
影响因子：
5.8
通讯作者：
BARELI, M
中科院分区：
文献类型：
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作者：
HUANG, SY;SINGH, RK;BARELI, M
本研究的目的是确定编码单核细胞趋化蛋白 MCP-1（也称为单核细胞趋化激活因子 MCAF TDCF 和 SMC-CF）的 JE/MCP-1 基因的表达是否可以影响肿瘤细胞的转移特性。高度转移性小鼠结肠癌 CT-26 细胞与不产生内源性 JE/MCP-1 蛋白的 BALB/c 小鼠同源，用 BCMGS-Neo 表达载体（对照）或含有全长 JE cDNA 的载体转染。 CT-26亲代细胞、CT-26 Neo和CT-26 JE/MCP-1阳性细胞被注射到同系小鼠或裸鼠中。 CT-26 JE/MCP 阳性细胞产生的肺转移明显减少。转移发生率的降低并不是由于转染细胞无法在肺脉管系统中停滞或细胞周期时间的差异所致。产生 JE/MCP-1 的 CT-26 细胞非常容易被用亚阈值浓度的脂多糖处理的同基因巨噬细胞裂解。此外，表达 JE/MCP-1 的细胞的培养上清液加上脂多糖可协同激活同系巨噬细胞的杀肿瘤特性。该活性被抗 JE/MCP-1 抗体阻断，表明 JE/MCP-1 分子参与了该过程。此外，将纯化的 JE/MCP-1 添加到含脂多糖的培养基中会导致巨噬细胞针对亲本 CT-26 细胞的显着激活。这些数据表明，除了其趋化特性外，JE/MCP-1 还可以与细菌内毒素协同作用，激活巨噬细胞，从而具有杀肿瘤作用，从而抑制转移。
The purpose of this study was to determine whether the expression of the JE/MCP-1 gene encoding for the monocyte chemottractant protein, MCP-1 (also known as monocyte chemotactic and activating factor MCAF TDCF and SMC-CF) can influence the metastatic properties of tumor cells. The highly metastatic murine colon carcinoma CT-26 cells, syngeneic to BALB/c mice that do not produce endogenous JE/MCP-1 protein, were transfected with a BCMGS-Neo expression vector (control) or a vector containing full-length JE cDNA. CT-26 parental cells, CT-26 Neo, and CT-26 JE/MCP-1-positive cells were injected into syngeneic or nude mice. The CT-26 JE/MCP-positive cells produced significantly fewer lung metastases. The decrease in incidence of metastasis was not due to the inability of the transfected cells to arrest in the lung vasculature or to differences in cell cycle time. CT-26 cells producing JE/MCP-1 were highly susceptible to lysis by syngeneic macrophages treated with subthreshold concentrations of lipopolysaccharide. In addition, culture supernatants of JE/MCP-1-expressing cells plus lipopolysaccharide synergistically activated tumoricidal properties in syngeneic macrophages. This activity was blocked by anti-JE/MCP-1 antibodies, indicating the involvement of the JE/MCP-1 molecule in this process. Moreover, purified JE/MCP-1 added to lipopolysaccharide-containing medium resulted in significant activation of macrophages against parental CT-26 cells. These data suggest that, in addition to its chemotactic properties, JE/MCP-1 can synergize with bacterial endotoxins to activate macrophages to become tumoricidal and, hence, could suppress metastasis.