Galectin‐1 Modulates Human Glioblastoma Cell Migration into the Brain Through Modifications to the Actin Cytoskeleton and Levels of Expression of Small GTPases

I. Camby, N. Belot, F. Lefranc, N. Sadeghi, Y. Launoit, H. Kaltner, S. Musette, F. Darro, A. Danguy, I. Salmon, H. Gabius, R. Kiss
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引用次数: 193

Abstract

We show that high-grade astrocytic tumors with high levels of galectin-1 expression are associated with dismal prognoses. The immunohistochemical analysis of galectin-1 expression of human U87 and U373 glioblastoma xenografts from the brains of nude mice revealed a higher level of galectin-1 expression in invasive areas rather than non-invasive areas of the xenografts. Nude mice intracranially grafted with U87 or U373 cells constitutively expressing low levels of galectin-1 (by stable transfection of an expression vector containing the antisense mRNA of galectin-1) had longer survival periods than those grafted with U87 or U373 cells expressing normal levels of galectin-1. Galectin-1 added to the culture media markedly and specifically increased cell motility levels in human neoplastic astrocytes. These effects are related to marked modifications in the organization of the actin cytoskeleton and the increase in small GTPase RhoA expression. All the data obtained indicate that galectin-1 enhances the migratory capabilities of tumor astrocytes and, therefore, their biological aggressiveness.
半乳糖凝集素- 1通过改变肌动蛋白细胞骨架和小gtp酶的表达水平调节人胶质母细胞瘤细胞向大脑的迁移
我们发现高水平半凝集素-1表达的高级别星形细胞肿瘤与预后不良相关。免疫组化分析裸鼠大脑移植的人U87和U373胶质母细胞瘤的半乳糖凝集素-1表达,发现半乳糖凝集素-1在移植物的侵袭区比非侵袭区表达水平更高。裸鼠颅内移植含有低水平半乳糖凝集素-1的U87或U373细胞(通过稳定转染含有半乳糖凝集素-1反义mRNA的表达载体)比移植含有正常水平半乳糖凝集素-1的U87或U373细胞的裸鼠存活时间更长。在培养基中添加半乳糖凝集素-1可显著提高人肿瘤星形胶质细胞的细胞运动水平。这些影响与肌动蛋白细胞骨架组织的显著改变和小GTPase RhoA表达的增加有关。所有得到的数据都表明半乳糖凝集素-1增强了肿瘤星形胶质细胞的迁移能力,从而增强了它们的生物侵袭性。
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