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 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.

Tumor-suppressive Maspin Functions as a Reactive Oxygen Species Scavenger

“…5B). In agreement with this, Cia et al (46) have also reported decreased proliferation rates with maspin overexpression in esophageal carcinoma. Also, NAC treatment reversed the oxidative stress phenotype of maspin-deficient or mutant maspin cells, thus indicating that proliferation is a result of increased ROS in these cells.…”

Mechanisms by Which Interleukin-6 Attenuates Cell Invasion and Tumorigenesis in Human Bladder Carcinoma Cells

“…Our study also represents the first report demonstrating the IL6-regulated expression of the E-cadherin, N-cadherin, and vimentin protein in bladder carcinoma cells. A recent study indicated that MASPIN-positive cells were resistant to EGF-induced EMT, suggesting that MASPIN may be involved in the EMT pathways in urothelial-bladder carcinoma [45]. The expression of NDRG1 has been shown to be significantly correlated with the expression of E-cadherin in prostate cancer [46].…”

Association Analysis of SERPINB5 Polymorphisms with HBV Clearance and HCC Occurrence in a Korean Population

“…SERPINB5 has been associated with prostate cancer, breast cancer (Shao et al, 2008), pancreas cancer (Kashima et al, 2008;Maass et al, 2001) and various types of carcinomas (Bal et al, 2008;Blandamura et al, 2006;Cai et al, 2009 with HCC occurrence, it had a low statistical power (40.8%) and haplotype frequency (0.052), meaning the susceptible population was of a small size and unreliable. Therefore, it is still unsure whether ht5 really had an association with HCC occurrence or was just a false positive association, thus the association may need to be studied again in the future with bigger sample number, preferably with a higher number of subjects that exhibit ht5 haplotypes.…”

“…However, SERPINB5 is a special case, which acts as a tumor suppressor gene instead of affecting protein pathways. SERPINB5 has previously shown the ability to suppress tumor cells in places such as bones, pancreas, and esophagus (Cai et al, 2009;Hall et al, 2008;Hong et al, 2009). From these findings, it can be inferred that SERPINB5 has a potent ability to suppress tumor cells.…”