Mammary serine protease inhibitor inhibits epithelial growth factor-induced epithelial-mesenchymal transition of esophageal carcinoma cells.

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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 1alpha than parental cells or empty vector transfected cells.

CONCLUSIONS:

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.

• Authors: Zhen Cai, Yuan Zhou, Ting Lei, Jen-Fu Chiu, Qing-Yu He
• Journal: Cancer (Cancer) Vol. 115 Issue 1 Pg. 36-48 (Jan 01 2009) ISSN: 0008-543X [Print] United States
• PMID: 19090015 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright (c) 2008 American Cancer Society.

Chemical References

• SERPIN-B5
• Serine Proteinase Inhibitors
• Serpins
• Epidermal Growth Factor

Topics

• Cell Differentiation
• Cell Line, Tumor
• Epidermal Growth Factor (pharmacology)
• Epithelial Cells
• Esophageal Neoplasms
• Humans
• Neoplasm Metastasis (prevention & control)
• Serine Proteinase Inhibitors (metabolism, physiology)
• Serpins (metabolism, physiology)
• Transfection