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Sulfatase 2 (SULF2) Monoclonal Antibody 5D5 Suppresses Human Cholangiocarcinoma Xenograft Growth Through Regulation of a SULF2-Platelet-Derived Growth Factor Receptor Beta-Yes-Associated Protein Signaling Axis

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Author(s)
Xin LuoNellie A. CampbellLi HeDaniel R. O'BrienMark S. SingerHassan Lemjabbar-AlaouiKeun Soo AhnRory SmootMichael S. TorbensonSteven D. RosenLewis R. Roberts
Keimyung Author(s)
Ahn, Keun Soo
Department
Dept. of Surgery (외과학)
Journal Title
Hepatology
Issued Date
2021
Volume
74
Issue
3
Abstract
Background and Aims:
Existing therapeutic approaches to treat cholangiocarcinoma (CCA) have limited effectiveness, prompting further study to develop therapies for CCA. We report a mechanistic role for the heparan sulfate editing enzyme sulfatase 2 (SULF2) in CCA pathogenesis.

Approach and Results:
In silico analysis revealed elevated SULF2 expression in human CCA samples, occurring partly through gain of SULF2 copy number. We examined the effects of knockdown or overexpression of SULF2 on tumor growth, chemoresistance, and signaling pathway activity in human CCA cell lines in vitro. Up-regulation of SULF2 in CCA leads to increased platelet-derived growth factor receptor beta (PDGFRβ)–Yes-associated protein (YAP) signaling activity, promoting tumor growth and chemotherapy resistance. To explore the utility of targeting SULF2 in the tumor microenvironment for CCA treatment, we tested an anti-SULF2 mouse monoclonal antibody, 5D5, in a mouse CCA xenograft model. Targeting SULF2 by monoclonal antibody 5D5 inhibited PDGFRβ–YAP signaling and tumor growth in the mouse xenograft model.

Conclusions:
These results suggest that SULF2 monoclonal antibody 5D5 or related agents may be potentially promising therapeutic agents in CCA.
Keimyung Author(s)(Kor)
안근수
Publisher
School of Medicine (의과대학)
Citation
Xin Luo et al. (2021). Sulfatase 2 (SULF2) Monoclonal Antibody 5D5 Suppresses Human Cholangiocarcinoma Xenograft Growth Through Regulation of a SULF2-Platelet-Derived Growth Factor Receptor Beta-Yes-Associated Protein Signaling Axis. Hepatology, 74(3), 1411–1428. doi: 10.1002/hep.31817
Type
Article
ISSN
1527-3350
Source
https://aasldpubs.onlinelibrary.wiley.com/doi/10.1002/hep.31817
DOI
10.1002/hep.31817
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/43801
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Surgery (외과학)
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