TY - JOUR
T1 - Polysialic acid facilitates tumor invasion by glioma cells
AU - Suzuki, Masami
AU - Suzuki, Misa
AU - Nakayama, Jun
AU - Suzuki, Atsushi
AU - Angata, Kiyohiko
AU - Chen, Shihao
AU - Sakai, Keiichi
AU - Hagihara, Kazuki
AU - Yamaguchi, Yu
AU - Fukuda, Minoru
N1 - Funding Information:
We thank Dr. Nobuyoshi Hiraoka for useful discussion, Dr. Edgar Ong for critical reading of the article, and Ms. Aleli Morse for organizing the article. The work was supported by grants R01 CA33895 (to M.F.) and R01 NS41332 (to Y.Y.) awarded by the National Institutes of Health and by grants-in-aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (Priority Area 14082201) and the Ministry of Health, Labor and Welfare of Japan (3rd Term Comprehensive Control Research for Cancer) (to J.N.).
PY - 2005/9
Y1 - 2005/9
N2 - 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.
AB - 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.
KW - Glioma
KW - NCAM
KW - Polysialic acid
KW - Polysialyltransferases
KW - Tumor invasion
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U2 - 10.1093/glycob/cwi071
DO - 10.1093/glycob/cwi071
M3 - Article
C2 - 15872150
AN - SCOPUS:24144436383
VL - 15
SP - 887
EP - 894
JO - Glycobiology
JF - Glycobiology
SN - 0959-6658
IS - 9
ER -