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: Misa Suzuki-Anekoji, Masami Suzuki, Tatsuya Kobayashi, Yoshiko Sato, Jun Nakayama, Atsushi Suzuki, Xingfeng Bao, Kiyohiko Angata, Minoru Fukuda
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 286 Issue 37 Pg. 32824-33 (Sep 16 2011) ISSN: 1083-351X [Electronic] United States
• PMID: 21784847 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Antibodies
• Antigens, Neoplasm
• Glucans
• Integrin beta1
• Neoplasm Proteins
• Focal Adhesion Protein-Tyrosine Kinases
• MAPK1 protein, human
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3

Topics

• Animals
• Antibodies (pharmacology)
• Antigens, Neoplasm (metabolism)
• Astrocytoma (metabolism, pathology)
• Brain Neoplasms (metabolism, pathology)
• Cell Line, Tumor
• Cell Movement
• Enzyme Activation (drug effects)
• Female
• Focal Adhesion Protein-Tyrosine Kinases (metabolism)
• Gene Expression Regulation, Neoplastic
• Glucans (metabolism)
• Humans
• Integrin beta1 (metabolism)
• Male
• Mice
• Mice, Nude
• Mitogen-Activated Protein Kinase 1 (metabolism)
• Mitogen-Activated Protein Kinase 3 (metabolism)
• Neoplasm Proteins (metabolism)
• Neoplasm Transplantation