SULF1 inhibits proliferation and invasion of esophageal squamous cell carcinoma cells by decreasing heparin-binding growth factor signaling.
BACKGROUND
Heparin-binding growth factor signaling is involved in the pathogenesis and development of human cancers. It can be regulated by sulfation of cell-surface heparan sulfate proteoglycans (HSPG). SULF1 is a heparin-degrading endosulfatase which can modulate the sulfation of HSPGs.


OBJECTIVE
The purpose of this study was to elucidate the role of SULF1 in modulating proliferation and invasion of esophageal squamous cell carcinoma (ESCC) by decreasing heparin-binding growth factor signaling.


METHODS
We restored SULF1 expression in the ESCC cell line KYSE150, and examined the effects of SULF1 expression on the proliferation and invasion of KYSE150 cells. In addition, we investigated the expression of SULF1 in human ESCC tissues and analyzed the correlation of SULF1 expression with clinicopathologic characteristics of ESCC.


RESULTS
Our study shows that re-expression of SULF1 in ESCC cell line results in the downregulation of hepatocyte growth factor-mediated activation of MAPK pathways with a resultant decrease in cell invasiveness. Cell proliferation was also inhibited in SULF1-transfected KYSE150 cells. Immunohistochemical assays reveal that SULF1 is expressed in nearly half of the human ESCC tissues but not in normal esophageal epithelial cells. SULF1 expression in human ESCC tissues is negatively correlated with tumor size and tumor invasion.


CONCLUSIONS
This study identified that SULF1 inhibits proliferation and invasion of ESCC by decreasing heparin-binding growth factor signaling and suggested that SULF1 plays an inhibiting role in the pathogenesis of ESCC.
Department of Gastroenterology, Beijing Digestive Disease Center, Beijing Friendship Hospital, Capital Medical University, Yong An Road 95, Beijing, 100050, China.
Chun-Tao
CT
Liu
Sheng-Tao
ST
Zhu
Peng
P
Li
Yong-Jun
YJ
Wang
Hao
H
Zhang
Shu-Tian
ST
Zhang
D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004938:Esophageal Neoplasms / Q000201:enzymology* / Q000473:pathology; D004947:Esophagus / Q000473:pathology; D005260:Female; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System; D008297:Male; D008875:Middle Aged; D015238:Sulfotransferases / Q000378:metabolism*
D005346:Fibroblast Growth Factors; C470791:SULF1 protein, human; D015238:Sulfotransferases