Abstract
Tumor suppressor maspin is a differentially regulated gene in the progression of many types of cancer. While the biological function of maspin in blocking tumor invasion and metastasis is consistent with the loss of maspin expression at the late stage of tumor progression, the differential expression and the biological significance of maspin in early stage of tumor progression appear to be complex and remain to be elucidated. In the current study, we examined the expression of maspin in 84 esophageal squamous cell carcinoma (ESCC) cases (stages I–III) and 55 non-tumor adjacent esophageal tissue specimens by immunohistochemical (IHC) staining. The correlation of maspin with clinicopathological parameters was analyzed. Compared to normal esophageal squamous tissue where 80% (47/55) of the cases expressed maspin at a low to moderate level, all ESCC specimens (100% (84/84)) were positive for maspin expression at a moderate to high level. ESCC with low or moderate maspin expression had significantly shorter postoperative survival rates compared to those that had high maspin expression (p<0.001). Since the correlation of maspin with ESCC histology and the correlation of maspin with ESCC prognosis seem to be at odds, we further investigated the biological function of maspin in ESCC using the established ESCC cell lines. The expression of maspin in five human esophageal squamous cancer cell lines (T12, E450, KYSE150, EC109, and KYSE510) was examined by the Western blot. ESCC cell line KYSE510 that did not express maspin and was stably transfected by maspin cDNA or an empty vector. The resulting transfected cells were characterized in vitro. Maspin expression significantly inhibited cell proliferation, motility and matrigel invasion. Taken together, our data suggest that the transient up-regulation of maspin in the early development of ESCC may be a defense mechanism against further transition towards more malignant phenotypes, ultimately slowing down ESCC tumor progression.
Highlights
Esophageal carcinoma, one of the most aggressive carcinomas of the gastrointestinal tract, is the eighth most common cause of cancer-related death worldwide [1,2]
We further investigated the biological function of maspin using established esophageal squamous cell carcinoma (ESCC) cell lines and showed an inhibitory effect of maspin on cell proliferation, motility, and invasion
To investigate whether the level or subcellular localization of maspin helps predict the survival of ESCC patients, ESCC tissues were collected from 84 stage I-III patients who were eligible for and underwent surgical resection between 2003 and 2007
Summary
Esophageal carcinoma, one of the most aggressive carcinomas of the gastrointestinal tract, is the eighth most common cause of cancer-related death worldwide [1,2]. The two main subtypes of esophageal carcinoma are adenocarcinoma and squamous cell carcinoma (ESCC), while the most commonly diagnosed esophageal cancer in China and other Asian countries is ESCC [3,4]. Specific biomarkers that are mechanistically involved in the progression of ESCC may significantly improve the accuracy of the prediction of patients’ survival. To this end, it is important to note that many of the molecular markers that are associated with specific pathological grades (diagnosis) have failed to serve as prognostic markers. The capacity of tumor cells to turn on tumor suppressive mechanisms, even though transitory, may translate into delayed tumor progression, and prolonged patients’ survival
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