CD24 promotes invasion of glioma cells in vivo
CD24 promotes invasion of glioma cells in vivo
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DOI：
10.1097/00005072-199908000-00002
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发表时间：
1999-08-01
影响因子：
3.2
通讯作者：
Paulus, W
中科院分区：
文献类型：
--
作者：
Senner, V;Sturm, A;Paulus, W
基于胶质瘤细胞表面表达的粘附分子介导脑侵袭的假设，我们在体外和体内研究了CD24对胶质瘤生长和迁移的影响。CD24是一种糖基磷脂酰肌醇锚定的、高度糖基化的粘附分子，在造血细胞和神经细胞中表达。我们在人胶质母细胞瘤中发现了CD24的免疫组织化学表达。然后，我们建立了C6大鼠胶质母细胞瘤细胞的克隆，其中小鼠CD24（也称为热稳定抗原）受到四环素应答启动子的控制。在四环素（1 μ g/ml）作用下，CD24下调20倍。体外迁移实验在基底膜制剂（基质）和髓磷脂上进行，髓磷脂是体内胶质瘤迁移的主要基质。与髓磷脂相比，细胞在基质上的运动性更强，而CD24的表达与运动性没有关系。然后将C6克隆移植到裸鼠纹状体中，并通过四环素（1 mg/ml）调节饮用水中CD24的表达。3周后，未接受四环素治疗的CD24阳性小鼠肿瘤显示肿瘤细胞弥漫性侵袭，其脑区面积比接受四环素治疗的CD24抑制小鼠肿瘤大10倍。这些数据表明，CD24在体内刺激胶质瘤的迁移，并提示这种粘附分子在人类胶质瘤弥漫性脑侵袭中发挥作用。
Based on the hypothesis that adhesion molecules expressed on the surface of glioma cells mediate brain invasion, we examined the effect of CD24 on growth and migration of gliomas in vitro and in vivo. CD24, a glycosylphosphatidyl inositol anchored, highly glycosylated adhesion molecule, is expressed in hematopoietic and neural cells. We found immunohistochemical expression of CD24 in human,glioblastomas. We then established a clone from C6 rat glioblastoma cells, where mouse CD24 (also called heat stable antigen) is under control of a tetracycline-responsive promoter. In the presence of tetracycline (1 mu g/ml) CD24 was downregulated by 20-fold. In vitro migration assays were performed on a basement membrane preparation (matrigel) and on myelin, the main substrates of in vivo glioma migration. While the cells were more motile on matrigel as compared with myelin, no relation between CD24 expression and motility was observed. We then transplanted the C6 clone into the striatum of nude mice and regulated CD24 expression via tetracycline in the drinking water (1 mg/ml). After 3 weeks, CD24 positive tumors of mice getting no tetracycline showed diffuse invasion of tumor cells in a brain area 10-fold larger than in CD24-suppressed tumors of mice receiving tetracycline. These data show that CD24 stimulates migration of gliomas in vivo and they suggest a role for this adhesion molecule in diffuse brain invasion of human gliomas.