Abstract
BackgroundWAP four-disulfide core domain protein 2 (WFDC2) shows a tumor-restricted upregulated pattern of expression in ovarian cancer.MethodsIn this study, we evaluated the role of WFCD2 in tumor mobility, invasion and metastasis of ovarian cancer in clinical tissue and in ovarian cancer cells, both in vitro and in vivo.ResultsOur results revealed WFCD2 was overexpressed in ovarian tissues, and the expression level of WFCD2 was associated with metastasis and lymph node metastasis. Higher expression of WFCD2 was also observed in aggressive HO8910-PM cells than in HO8910 cells, and WFCD2 knockdown halted cell migration, invasion, tumorigenicity and metastasis in ovarian cancer cells, both in vitro and in vivo. Knockdown of WFDC2 induced the down-regulation of ICAM-1, CD44, and MMP2.ConclusionIn summary, our work demonstrates that WFCD2 promotes metastasis in ovarian cancer. These findings suggest that WFCD2 plays a critical role in promoting metastasis and may constitute a potential therapeutic target of ovarian cancer.
Highlights
WAP four-disulfide core domain protein 2 (WFDC2) shows a tumor-restricted upregulated pattern of expression in ovarian cancer
Increased expression of WFCD2 correlated with the progression and peritoneal metastasis of human ovarian cancer To examine the potential clinical relevance of WFCD2 to ovarian cancer progression, the human ovarian cancer tissues were derived from patients with progressive ovarian disease to investigate WFCD2 expression and its association with different clinicopathological parameters
The WFCD2 staining score of carcinomas is significantly higher than that of nonneoplastic ovarian tissues, which revealed a correlation between WFCD2 expression levels and ovarian cancer progression (Fig. 1b), while no significence had been observed between high-grade carcinomas and low-grade carcinomas
Summary
WAP four-disulfide core domain protein 2 (WFDC2) shows a tumor-restricted upregulated pattern of expression in ovarian cancer. Ovarian cancer is one of the most common gynecological cancers worldwide. With the highest mortality rate of all gynecologic cancers, ovarian cancer is very problematic to treat. Tumor progression is generally associated with extensive tissue remodeling to provide a proper environment for tumor growth, angiogenesis, invasion, and eventual metastasis of cancer cells. A recent study has identified WFCD2 as a new member of the group of serine protease inhibitors belonging to the WAP family. While prior research indicated a direct linkage between WFCD2 expression and cell proliferation [6, 7], its physiological and pathological mechanisms in tumorigenesis and metastasis have not been clearly elucidated
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