Mammary serine protease inhibitor inhibits epithelial growth factor-induced epithelial-mesenchymal transition of esophageal carcinoma cells.
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.
Cai
Zhen
Z
Clinical Laboratory, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Zhou
Yuan
Y
Lei
Ting
T
Chiu
Jen-Fu
JF
He
Qing-Yu
QY
D002454:Cell Differentiation; D045744:Cell Line, Tumor; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004847:Epithelial Cells; D004938:Esophageal Neoplasms; D006801:Humans; D009362:Neoplasm Metastasis / Q000517:prevention & control; D015842:Serine Proteinase Inhibitors / Q000378:metabolism / Q000502:physiology*; D015843:Serpins / Q000378:metabolism* / Q000502:physiology; D014162:Transfection
C085344:SERPIN-B5; D015842:Serine Proteinase Inhibitors; D015843:Serpins; D004815:Epidermal Growth Factor