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Role of GalNAc4S-6ST in Astrocytic Tumor Progression
Kobayashi, Tatsuya
Yan, Huimin
Kurahashi, Yasuhiro
Ito, Yuki
Maeda, Hiroshi
Tada, Tsuyoshi
Hongo, Kazuhiro
Nakayama, Jun
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 xi (PTP xi) 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 PTP xi 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.
Article
PLOS ONE. 8(1):e54278 (2013)
journal article
PUBLIC LIBRARY SCIENCE
2013-01-16
application/pdf
PLOS ONE
1
8
e54278
1932-6203
https://soar-ir.repo.nii.ac.jp/record/19062/files/Role_of_GalNAc4S-6ST_in_Astrocytic_Tumor_Progression.pdf
eng
23349846
https://pubmed.ncbi.nlm.nih.gov/23349846
10.1371/journal.pone.0054278
https://doi.org/10.1371/journal.pone.0054278
© 2013 Kobayashi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.