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Mammary serine protease inhibitor inhibits epithelial growth factor-induced epithelial-mesenchymal transition of esophageal carcinoma cells
Article first published online: 17 DEC 2008
Copyright © 2008 American Cancer Society
Volume 115, Issue 1, pages 36–48, 1 January 2009
How to Cite
Cai, Z., Zhou, Y., Lei, T., Chiu, J.-F. and He, Q.-Y. (2009), Mammary serine protease inhibitor inhibits epithelial growth factor-induced epithelial-mesenchymal transition of esophageal carcinoma cells. Cancer, 115: 36–48. doi: 10.1002/cncr.23991
- Issue published online: 29 DEC 2008
- Article first published online: 17 DEC 2008
- Manuscript Accepted: 1 AUG 2008
- Manuscript Revised: 15 JUL 2008
- Manuscript Received: 13 MAY 2008
- epithelial-mesenchymal transition;
- esophageal squamous cell carcinoma;
- mammary serine protease inhibitor;
By using proteomic technology, the authors previously observed the substantial down-regulation of mammary serine protease inhibitor (maspin) in esophageal squamous cell carcinoma and metastases. In the current study, they examined the effects of maspin re-expression in a maspin-null esophageal cancer cell line EC109 and also investigated the underlying mechanism.
A cell line with stable maspin expression was established. An epithelial growth factor (EGF)-induced epithelial-mesenchymal transition (EMT) model was used to mimic some aspects of the metastatic process in vitro. The effects of maspin reintroduction on EGF-induced EMT and cell growth characteristics were evaluated. Comparative proteomic analysis of transfected cells versus parental cells was then performed to explore the potential mechanism.
The introduction of maspin into EC109 cells was able to inhibit EGF-induced EMT and altered cell growth characteristics, including the serum dependence, proliferative response to EGF stimulation, and colony formation ability in soft agar, indicating a conversion from a malignant phenotype to a benign phenotype. Proteomic analysis revealed a significant down-regulation of a group of glycolytic enzymes in maspin-transfected cells. In addition, maspin-transfected cells expressed much lower levels of hypoxia-inducible factor 1α than parental cells or empty vector transfected cells.
Maspin exhibited a metastasis-suppressive effect, which may be a consequence of the reversal of the malignant phenotype of EC109 cells. The switch of cellular metabolic phenotype to low glycolysis by the gain of maspin function may play a key role in the process. This finding provides additional evidence of the tumor metastasis-suppressive activity of maspin and may indicate a new direction for future studies of the mechanism of maspin. Cancer 2009. © 2008 American Cancer Society.