DSE promotes aggressive glioma cell phenotypes by enhancing HB-EGF/ErbB signaling.
Remodeling of the extracellular matrix (ECM) in the tumor microenvironment promotes glioma progression. Chondroitin sulfate (CS) proteoglycans appear in the ECM and on the cell surface, and can be catalyzed by dermatan sulfate epimerase to form chondroitin sulfate/dermatan sulfate (CS/DS) hybrid cha...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2018-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5986151?pdf=render |
| _version_ | 1811266312020688896 |
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| author | Wen-Chieh Liao Chih-Kai Liao You-Huan Tsai To-Jung Tseng Li-Ching Chuang Chyn-Tair Lan Hung-Ming Chang Chiung-Hui Liu |
| author_facet | Wen-Chieh Liao Chih-Kai Liao You-Huan Tsai To-Jung Tseng Li-Ching Chuang Chyn-Tair Lan Hung-Ming Chang Chiung-Hui Liu |
| author_sort | Wen-Chieh Liao |
| collection | DOAJ |
| description | Remodeling of the extracellular matrix (ECM) in the tumor microenvironment promotes glioma progression. Chondroitin sulfate (CS) proteoglycans appear in the ECM and on the cell surface, and can be catalyzed by dermatan sulfate epimerase to form chondroitin sulfate/dermatan sulfate (CS/DS) hybrid chains. Dermatan sulfate epimerase 1 (DSE) is overexpressed in many types of cancer, and CS/DS chains mediate several growth factor signals. However, the role of DSE in gliomas has never been explored. In the present study, we determined the expression of DSE in gliomas by consulting a public database and conducting immunohistochemistry on a tissue array. Our investigation revealed that DSE was upregulated in gliomas compared with normal brain tissue. Furthermore, high DSE expression was associated with advanced tumor grade and poor survival. We found high DSE expression in several glioblastoma cell lines, and DSE expression directly mediated DS chain formation in glioblastoma cells. Knockdown of DSE suppressed the proliferation, migration, and invasion of glioblastoma cells. In contrast, overexpression of DSE in GL261 cells enhanced these malignant phenotypes and in vivo tumor growth. Interestingly, we found that DSE selectively regulated heparin-binding EGF-like growth factor (HB-EGF)-induced signaling in glioblastoma cells. Inhibiting epidermal growth factor receptor (EGFR) and ErbB2 with afatinib suppressed DSE-enhanced malignant phenotypes, establishing the critical role of the ErbB pathway in regulating the effects of DSE expression. This evidence indicates that upregulation of DSE in gliomas contributes to malignant behavior in cancer cells. We provide novel insight into the significance of DS chains in ErbB signaling and glioma pathogenesis. |
| first_indexed | 2024-04-12T20:40:59Z |
| format | Article |
| id | doaj.art-e7fb21f1722a4d59b5cef145fb9e65cb |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T20:40:59Z |
| publishDate | 2018-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-e7fb21f1722a4d59b5cef145fb9e65cb2022-12-22T03:17:25ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01136e019836410.1371/journal.pone.0198364DSE promotes aggressive glioma cell phenotypes by enhancing HB-EGF/ErbB signaling.Wen-Chieh LiaoChih-Kai LiaoYou-Huan TsaiTo-Jung TsengLi-Ching ChuangChyn-Tair LanHung-Ming ChangChiung-Hui LiuRemodeling of the extracellular matrix (ECM) in the tumor microenvironment promotes glioma progression. Chondroitin sulfate (CS) proteoglycans appear in the ECM and on the cell surface, and can be catalyzed by dermatan sulfate epimerase to form chondroitin sulfate/dermatan sulfate (CS/DS) hybrid chains. Dermatan sulfate epimerase 1 (DSE) is overexpressed in many types of cancer, and CS/DS chains mediate several growth factor signals. However, the role of DSE in gliomas has never been explored. In the present study, we determined the expression of DSE in gliomas by consulting a public database and conducting immunohistochemistry on a tissue array. Our investigation revealed that DSE was upregulated in gliomas compared with normal brain tissue. Furthermore, high DSE expression was associated with advanced tumor grade and poor survival. We found high DSE expression in several glioblastoma cell lines, and DSE expression directly mediated DS chain formation in glioblastoma cells. Knockdown of DSE suppressed the proliferation, migration, and invasion of glioblastoma cells. In contrast, overexpression of DSE in GL261 cells enhanced these malignant phenotypes and in vivo tumor growth. Interestingly, we found that DSE selectively regulated heparin-binding EGF-like growth factor (HB-EGF)-induced signaling in glioblastoma cells. Inhibiting epidermal growth factor receptor (EGFR) and ErbB2 with afatinib suppressed DSE-enhanced malignant phenotypes, establishing the critical role of the ErbB pathway in regulating the effects of DSE expression. This evidence indicates that upregulation of DSE in gliomas contributes to malignant behavior in cancer cells. We provide novel insight into the significance of DS chains in ErbB signaling and glioma pathogenesis.http://europepmc.org/articles/PMC5986151?pdf=render |
| spellingShingle | Wen-Chieh Liao Chih-Kai Liao You-Huan Tsai To-Jung Tseng Li-Ching Chuang Chyn-Tair Lan Hung-Ming Chang Chiung-Hui Liu DSE promotes aggressive glioma cell phenotypes by enhancing HB-EGF/ErbB signaling. PLoS ONE |
| title | DSE promotes aggressive glioma cell phenotypes by enhancing HB-EGF/ErbB signaling. |
| title_full | DSE promotes aggressive glioma cell phenotypes by enhancing HB-EGF/ErbB signaling. |
| title_fullStr | DSE promotes aggressive glioma cell phenotypes by enhancing HB-EGF/ErbB signaling. |
| title_full_unstemmed | DSE promotes aggressive glioma cell phenotypes by enhancing HB-EGF/ErbB signaling. |
| title_short | DSE promotes aggressive glioma cell phenotypes by enhancing HB-EGF/ErbB signaling. |
| title_sort | dse promotes aggressive glioma cell phenotypes by enhancing hb egf erbb signaling |
| url | http://europepmc.org/articles/PMC5986151?pdf=render |
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