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Mammary serine protease inhibitor inhibits epithelial growth factor‐induced epithelial‐mesenchymal transition of esophageal carcinoma cells
Author(s) -
Cai Zhen,
Zhou Yuan,
Lei Ting,
Chiu JenFu,
He QingYu
Publication year - 2008
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.23991
Subject(s) - maspin , epithelial–mesenchymal transition , transfection , cancer research , cell culture , epidermal growth factor , biology , cell growth , metastasis , cancer cell , cancer , medicine , genetics
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 1α 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. Cancer 2009. © 2008 American Cancer Society.