Gene expression of neural cell adhesion molecule L1 in malignant gliomas and biological significance of L1 in glioma invasion.

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.