This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Li, W. Articles by Liu, Z. Search for Related Content PubMed PubMed Citation Articles by Li, W. Articles by Liu, Z.

Overexpression of Stefin A in Human Esophageal Squamous Cell Carcinoma Cells Inhibits Tumor Cell Growth, Angiogenesis, Invasion, and Metastasis

Authors' Affiliation: National Laboratory of Molecular Oncology, Cancer Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China

Requests for reprints: Zhihua Liu, National Laboratory of Molecular Oncology, Cancer Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China. Phone: 86-10-67723789; Fax: 86-10-67723789; E-mail: liuzh{at}pubem.cicams.ac.cn.

Purpose: Evidence is accumulating that an inverse correlation exists between stefin A level and malignant progression. The aim of this study is to investigate the role of stefin A in human esophageal squamous cell carcinoma cells and to evaluate the possibility of stefin A for cancer therapy.

Experimental Design: We stably transfected stefin A cDNA into human EC9706 or KYSE150 esophageal squamous cell carcinoma cells. Subsequently, we evaluated the effect of stefin A overexpression on cell growth, cathepsin B activity, cell motility and invasion, tumor growth, and metastasis. Immunoanalysis was done to assess the expression of factor VIII and to support the localization of stefin A and cathepsin B. We also evaluated the effect of CA074Me, a selective membrane-permeant cathepsin B inhibitor.

Results: Both transfection of stefin A and treatment with 10 µmol/L CA074Me significantly reduced cathepsin B activity and inhibited the Matrigel invasion. Combination of both further reduced cathepsin B activity and inhibited the Matrigel invasion. Overexpression of stefin A delayed the in vitro and in vivo growth of cells and significantly inhibited lung metastasis compared with 50% of lung metastasis in xenograft mice from EC9706 or empty vector cells. Transfection with stefin A showed a dramatic reduction of factor VIII staining in the tumors of xenograft mice.

Conclusions: Our data strongly indicate that stefin A plays an important role in the growth, angiogenesis, invasion, and metastasis of human esophageal squamous cell carcinoma cells and suggest that stefin A may be useful in cancer therapy.

This article has been cited by other articles:

				Y. Song, C. Zhao, L. Dong, M. Fu, L. Xue, Z. Huang, T. Tong, Z. Zhou, A. Chen, Z. Yang, et al. Overexpression of cyclin B1 in human esophageal squamous cell carcinoma cells induces tumor cell invasive growth and metastasis Carcinogenesis, February 1, 2008; 29(2): 307 - 315. [Abstract] [Full Text] [PDF]