Effect of endothelin-1 in esophageal squamous cell carcinoma invasion and its correlation with cathepsin B.
OBJECTIVE
To investigate the effect of endothelin-1 in the invasion of esophageal cancer and determine whether cathepsin B plays a role in the course.


METHODS
Western blotting was employed to detect the expression of ET-1 protein in 75 samples of esophageal squamous cell cancer and matched normal esophageal mucosa. Bosentan, a dual ET (A/B)-receptor antagonist, was used to inhibit the binding of endothelin-1 and its receptors and cut down its biological role. In vitro matrigel invasion assays were made to show the invasive ability of esophageal cancer cells with and without bosentan. Subsequently, we evaluated cathepsin B activity and expression in EC9706 cell with and without bosentan.


RESULTS
We found 74.7% (56/75) tumors had an overexpression of ET-1 protein by Western blotting. Bosentan significantly inhibited matrigel invasion of cancer cells in vitro. EC9706 cells have a positive expression of cathepsin B protein, and bosentan can down-regulate its expression and activity.


CONCLUSIONS
Endothelin-1 may enhance the invasive ability of human esophageal cancer cells, and its role is correlated with cathepsin B.
Department of Thoracic Surgery, Peking University First Hospital, No. 8, Xishiku Street, Beijing 100034, China. jiaowenjie@163.com
Wen-Jie
WJ
Jiao
Jing
J
Xu
Hao
H
Pan
Tian-You
TY
Wang
Yi
Y
Shen
D000959:Antihypertensive Agents / Q000494:pharmacology; D000077300:Bosentan; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D002401:Cathepsin B / Q000096:biosynthesis* / Q000502:physiology; D045744:Cell Line, Tumor; D003094:Collagen / Q000737:chemistry; D018450:Disease Progression; D004338:Drug Combinations; D019332:Endothelin-1 / Q000502:physiology*; D004938:Esophageal Neoplasms / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007797:Laminin / Q000737:chemistry; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic; D011509:Proteoglycans / Q000737:chemistry; D013449:Sulfonamides / Q000494:pharmacology
D000959:Antihypertensive Agents; D004338:Drug Combinations; D019332:Endothelin-1; D007797:Laminin; D011509:Proteoglycans; D013449:Sulfonamides; C059485:matrigel; D003094:Collagen; D002401:Cathepsin B; D000077300:Bosentan