Izumoto S, Ohnishi T, Arita N, Hiraga S, Taki T, Hayakawa T
Department of Neurosurgery, Osaka University Medical School, Japan.
Cancer Res. 1996 Mar 15;56(6):1440-4.
Neural cell adhesion molecule L1 is a member of the immunoglobulin superfamily that is expressed in the nervous system. Its functions have been mainly studied in vitro using premature neuronal cells. We show that all glioma cells tested, as well as normal glia cells, express a short type of L1, L1cs mRNA. The expression of L1 protein in glioma cells was confirmed by Western blotting and flow cytometric analysis. Migration assay showed that C6 glioma cells were stimulated to migrate to soluble L1 and L1cs released from L1- or L1cs-transfected fibroblast cells. The L1-stimulated migration was significantly inhibited by antibody that recognizes the immunoglobulin C2-like domain of L1. However, antibodies that recognize the fibronectin type III-like domain and the cytoplasmic (IC) domain of L1 had no effect on migration. Our in vivo migration study demonstrated the migration of L1 on C6 glioma cells that had been transfected in rat brains. These results suggest that L1cs expressed on glioma cells may play an important role in the adhesion and migration of glioma cells by homophilic binding (probably through the extracellular immunoglobulin C2 domain of L1) and that L1cs participates in tumor invasion along neuronal fibers.
神经细胞黏附分子L1是免疫球蛋白超家族的成员，在神经系统中表达。其功能主要在体外使用未成熟神经元细胞进行研究。我们发现，所有测试的胶质瘤细胞以及正常神经胶质细胞均表达一种短型L1，即L1cs mRNA。通过蛋白质印迹法和流式细胞术分析证实了胶质瘤细胞中L1蛋白的表达。迁移试验表明，C6胶质瘤细胞被刺激向从L1或L1cs转染的成纤维细胞释放的可溶性L1和L1cs迁移。识别L1免疫球蛋白C2样结构域的抗体显著抑制了L1刺激的迁移。然而，识别L1纤连蛋白III样结构域和细胞质（IC）结构域的抗体对迁移没有影响。我们的体内迁移研究证明了在大鼠脑中已转染的C6胶质瘤细胞上L1的迁移。这些结果表明，胶质瘤细胞上表达的L1cs可能通过同源性结合（可能通过L1的细胞外免疫球蛋白C2结构域）在胶质瘤细胞的黏附和迁移中起重要作用，并且L1cs参与沿神经纤维的肿瘤侵袭。
