Glycobiology Advance Access originally published online on May 4, 2005
Glycobiology 2005 15(9):887-894; doi:10.1093/glycob/cwi071
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Polysialic acid facilitates tumor invasion by glioma cells
4 Glycobiology, Cancer Research Center, The Burnham Institute, La Jolla, CA 92037; 5 Department of Pathology, Shinshu University School of Medicine, Matsumoto 390-8621, Japan; 6 Department of Neurosurgery, Shinshu University School of Medicine, Matsumoto 390-8621, Japan; 7 Developmental Neurobiology Programs, Cancer Research Center, The Burnham Institute, La Jolla, CA 92037
1 These authors contributed equally to this work.
2 To whom correspondence should be addressed; e-mail: minoru{at}burnham.org
3 Present address: Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo 160-8582, Japan
Received on March 15, 2005; revised on April 26, 2005; accepted on April 27, 2005
Polysialic acid (PSA) is thought to attenuate neural cell adhesion molecule (NCAM) adhesion, thereby facilitating neural cell migration and regeneration. Although the expression of PSA has been shown to correlate with the progression of certain tumors such as small cell lung carcinoma, there have been no studies to determine the roles of PSA in gliomas, the most common type of primary brain tumor in humans. In this study, we first revealed that among patients with glioma, PSA was detected more frequently in diffuse astrocytoma cells, which spread extensively. To determine directly the role of PSA in glioma cell invasion, we transfected C6 glioma cells with polysialyltransferases to express PSA. In those transfected cells, PSA is attached mainly to NCAM-140, whereas the mock-transfected C6 cells express equivalent amounts of PSA-free NCAM-140. Both PSA negative and positive C6 cell lines exhibited almost identical growth rates measured in vitro. However, PSA positive C6 cells exhibited increased invasion to the corpus callosum, where the mock-transfected C6 glioma cells rarely invaded when inoculated into the brain. By contrast, the invasion to the corpus callosum by both the mock-transfected and PSA positive C6 cells was observed in NCAM-deficient mice. These results combined indicate that PSA facilitates tumor invasion of glioma in the brain, and that NCAM–NCAM interaction is likely attenuated in the PSA-mediated tumor invasion.
Key words: polysialic acid / glioma / tumor invasion / NCAM / polysialyltransferases
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