title: HNK-1 glycan functions as a tumor suppressor for astrocytic tumor.
abstract: Astrocytic tumor is the most prevalent primary brain tumor. However, the role of cell surface carbohydrates in astrocytic tumor invasion is not known. In a previous study, we showed that polysialic acid facilitates astrocytic tumor invasion and thereby tumor progression. Here, we examined the role of HNK-1 glycan in astrocytic tumor invasion. A Kaplan-Meier analysis of 45 patients revealed that higher HNK-1 expression levels were positively associated with increased survival of patients. To determine the role of HNK-1 glycan, we transfected C6 glioma cells, which lack HNK-1 glycan expression, with β1,3-glucuronyltransferase-P cDNA, generating HNK-1-positive cells. When these cells were injected into the mouse brain, the resultant tumors were 60% smaller than tumors emerging from injection of the mock-transfected HNK-1-negative C6 cells. HNK-1-positive C6 cells also grew more slowly than mock-transfected C6 cells in anchorage-dependent and anchorage-independent assays. C6-HNK-1 cells migrated well after treatment of anti-β1 integrin antibody, whereas the same treatment inhibited cell migration of mock-transfected C6 cells. Similarly, α-dystroglycan containing HNK-1 glycan is different from those containing the laminin-binding glycans, supporting the above conclusion that C6-HNK-1 cells migrate independently from β1-integrin-mediated signaling. Moreover, HNK-1-positive cells exhibited attenuated activation of ERK 1/2 compared with mock-transfected C6 cells, whereas focal adhesion kinase activation was equivalent in both cell types. Overall, these results indicate that HNK-1 glycan functions as a tumor suppressor.
authors.affiliation: Tumor Microenvironment Program, Cancer Research Center, Sanford-Burnham Medical Research Institute, La Jolla, California 92037, USA.
authors.forename: Misa
authors.initials: M
authors.lastname: Suzuki-Anekoji
authors.forename: Masami
authors.initials: M
authors.lastname: Suzuki
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Sato
authors.forename: Jun
authors.initials: J
authors.lastname: Nakayama
authors.forename: Atsushi
authors.initials: A
authors.lastname: Suzuki
authors.forename: Xingfeng
authors.initials: X
authors.lastname: Bao
authors.forename: Kiyohiko
authors.initials: K
authors.lastname: Angata
authors.forename: Minoru
authors.initials: M
authors.lastname: Fukuda
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D000951:Antigens, Neoplasm / Q000378:metabolism*; D001254:Astrocytoma / Q000378:metabolism* / Q000473:pathology; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D005936:Glucans / Q000378:metabolism*; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D008297:Male; D051379:Mice; D008819:Mice, Nude; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D009368:Neoplasm Transplantation
chemical_list: D000906:Antibodies; D000951:Antigens, Neoplasm; D005936:Glucans; D019012:Integrin beta1; D009363:Neoplasm Proteins; D051416:Focal Adhesion Protein-Tyrosine Kinases; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3