PUBLICATION
Expression and function of chondroitin 4-sulfate and chondroitin 6-sulfate in human glioma
- Authors
- Pan, H., Xue, W., Zhao, W., Schachner, M.
- ID
- ZDB-PUB-200108-18
- Date
- 2019
- Source
- FASEB journal : official publication of the Federation of American Societies for Experimental Biology 34(2): 2853-2868 (Journal)
- Registered Authors
- Schachner, Melitta
- Keywords
- chondroitin 4-sulfate, chondroitin 6-sulfate, glioma, invasion, migration
- MeSH Terms
-
- Adolescent
- Adult
- Aged
- Animals
- Cell Line, Tumor
- Child
- Child, Preschool
- Chondroitin Sulfates/biosynthesis*
- Chondroitin Sulfates/genetics
- Female
- Gene Expression Regulation, Neoplastic*
- Glioma/genetics
- Glioma/metabolism*
- Glioma/pathology
- Humans
- Male
- Middle Aged
- Neoplasm Proteins/biosynthesis*
- Neoplasm Proteins/genetics
- Signal Transduction*
- Zebrafish/genetics
- Zebrafish/metabolism
- Zebrafish Proteins/biosynthesis
- Zebrafish Proteins/genetics
- PubMed
- 31908019 Full text @ FASEB J.
Citation
Pan, H., Xue, W., Zhao, W., Schachner, M. (2019) Expression and function of chondroitin 4-sulfate and chondroitin 6-sulfate in human glioma. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 34(2):2853-2868.
Abstract
Key molecules promoting migration and invasion exist in the extracellular matrix, and include chondroitin 4-sulfate (C4S) and chondroitin 6-sulfate (C6S), functionally important carbohydrate chains of chondroitin sulfate proteoglycans that participate in regulating cancer development. Here, we show that C4S and C6S expression is upregulated in human glioma tissues, when compared to normal brain tissue, and that the extent of upregulation positively correlated with glioma malignancy. Treatment of cultured glioma cells with C4S and C6S enhanced cell viability, migration, and invasion, increased MMP-2 and MMP-9 levels, enhanced N-cadherin, but reduced E-cadherin expression. Inhibition of expression of the two CS synthetic enzymes chondroitin 4-O-sulfotransferase-1 (C4ST-1/CHST11) and chondroitin 6-O-sulfotransferase-1 (C6ST-1/CHST3) suppressed cell viability, migration and invasion, reduced MMP-2 and MMP-9 expression, and reduced N-cadherin expression, but increased E-cadherin levels. The C4S- and C6S-enhanced epithelial-to-mesenchymal transition and expression of MMP-2 occurred via activation of the PI3K/AKT signaling pathway, known to be involved in promoting cell migration and invasion. In immune-deficient larval zebrafish, C4S and C6S increased the numbers of viable tumor cells, thereby promoting glioma cell proliferation. The present observations point to a novel role of C4S and C6S in human glioma cell functions, thus possibly representing targets in glioma therapy.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping