Role of GalNAc4S-6ST in astrocytic tumor progression.

Abstract

N-Acetylgalactosamine 4-sulfate 6-O-sulfotransferase (GalNAc4S-6ST) is the sulfotransferase responsible for biosynthesis of highly sulfated chondroitin sulfate CS-E. Although involvements of CS-E in neuronal cell functions have been extensively analyzed, the role of GalNAc4S-6ST in astrocytic tumor progression remains unknown. Here, we reveal that GalNAc4S-6ST transcripts were detected in astrocytic tumors derived from all 30 patients examined using quantitative reverse transcription-PCR analysis. Patients with high GalNAc4S-6ST mRNA expression had significantly worse outcome compared with patients with low expression, and multivariate survival analysis disclosed that GalNAc4S-6ST is an independent poor prognostic factor for astrocytic tumors. We then tested whether CS-E enhanced haptotaxic migration of glioblastoma U251-MG cells that endogenously express both the CS-E's scaffold tyrosine phosphatase ζ (PTPζ) and GalNAc4S-6ST, in the presence of CS-E's preferred ligands, pleiotrophin (PTN) or midkine (MK), using a modified Boyden chamber method. Haptotaxic stimulation of cell migration by PTN was most robust on control siRNA-transfected U251-MG cells, while that enhancing effect was cancelled following transduction of GalNAc4S-6ST siRNA. Similar results were obtained using MK, suggesting that both PTN and MK enhance migration of U251-MG cells by binding to CS-E. We also found that PTPζ as well as PTN and MK were frequently expressed in astrocytic tumor cells. Thus, our findings indicate that GalNAc4S-6ST mRNA expressed by astrocytic tumor cells is associated with poor patient prognosis likely by enhancing CS-E-mediated tumor cell motility in the presence of PTN and/or MK.

• Authors: Tatsuya Kobayashi, Huimin Yan, Yasuhiro Kurahashi, Yuki Ito, Hiroshi Maeda, Tsuyoshi Tada, Kazuhiro Hongo, Jun Nakayama
• Journal: PloS one (PLoS One) Vol. 8 Issue 1 Pg. e54278 ( 2013) ISSN: 1932-6203 [Electronic] United States
• PMID: 23349846 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Carrier Proteins
• Cytokines
• pleiotrophin
• Midkine
• Chondroitin Sulfates
• N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase
• Sulfotransferases
• Receptor-Like Protein Tyrosine Phosphatases, Class 5

Topics

• Adolescent
• Adult
• Aged
• Astrocytoma (genetics, metabolism, pathology)
• Brain Neoplasms (genetics, metabolism, pathology)
• Carrier Proteins (metabolism)
• Cell Line, Tumor
• Child
• Child, Preschool
• Chondroitin Sulfates (metabolism)
• Cytokines (metabolism)
• Disease Progression
• Female
• Gene Expression Regulation, Enzymologic
• Gene Expression Regulation, Neoplastic
• Humans
• In Situ Hybridization
• Male
• Middle Aged
• Midkine
• Multivariate Analysis
• Prognosis
• Receptor-Like Protein Tyrosine Phosphatases, Class 5 (metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Sulfotransferases (genetics, metabolism)
• Survival Analysis