Mammary Serine Protease Inhibitor Inhibits Epithelial Growth Factor-induced Epithelial-Mesenchymal Transition of Esophageal Carcinoma Cells
Mammary Serine Protease Inhibitor Inhibits Epithelial Growth Factor-induced Epithelial-Mesenchymal Transition of Esophageal Carcinoma Cells
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DOI：
10.1002/cncr.23991
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发表时间：
2009-01-01
期刊：
影响因子：
6.2
通讯作者：
He, Qing-Yu
中科院分区：
文献类型：
--
作者：
Cai, Zhen;Zhou, Yuan;He, Qing-Yu
背景：通过使用蛋白质组学技术，作者先前观察到乳腺丝氨酸蛋白酶抑制剂（maspin）在食管鳞状细胞癌和转移瘤中的大幅下调。在当前的研究中，他们检查了 maspin 重新表达在 maspin 缺失的食管癌细胞系 EC109 中的影响，并研究了其潜在机制。方法：建立稳定表达maspin的细胞系。使用上皮生长因子（EGF）诱导的上皮-间质转化（EMT）模型来模拟体外转移过程的某些方面。评估了 maspin 重新引入对 EGF 诱导的 EMT 和细胞生长特性的影响。然后对转染细胞与亲代细胞进行比较蛋白质组学分析，以探索潜在的机制。结果：将maspin引入EC109细胞能够抑制EGF诱导的EMT并改变细胞生长特性，包括血清依赖性、对EGF刺激的增殖反应以及软琼脂中的集落形成能力，表明从恶性表型向良性表型的转变。蛋白质组分析揭示了 maspin 转染细胞中一组糖酵解酶的显着下调。此外，maspin转染的细胞表达的缺氧诱导因子1α水平比亲本细胞或空载体转染的细胞低得多。结论：Maspin表现出转移抑制作用，这可能是逆转EC109细胞恶性表型的结果。通过获得 maspin 功能将细胞代谢表型转变为低糖酵解可能在此过程中发挥关键作用。这一发现为maspin的肿瘤转移抑制活性提供了额外的证据，并可能为maspin机制的未来研究指明新的方向。癌症 2009；115：36-48。 (C) 2008 年美国癌症协会。
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 1 alpha 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;115:36-48. (C) 2008 American Cancer Society.