5176

SERPINF1

BACKGROUND: Pigment epithelium-derived factor (PEDF) has been reported to inhibit angiogenesis in bladder cancer, but whether it modulates epithelial-mesenchymal transition (EMT) remains unknown. METHODS: We have included 68 samples of non-muscle invasive bladder cancer in this study. Immunohistochemistry was performed in all sample sections for expressions of PEDF, SNAI2, Vimentin and E-cadherin, which were quantified and The EMT Index (EMTi) was calculated by Vimentin/E-cadherin. Levels of expression were studied for correlations with clinicopathological parameters. RESULTS: Patients were grouped with high (EMTiEMTi>1) EMT level for comparisons of clinicopathological parameters. In the univariate analysis, EMT level was shown to be significantly associated with tumor onset and PEDF level, but not with gender, occurrence, stage, grade, or SNAI2 level. Further multivariate analysis revealed that PEDF level was significantly negatively correlated with EMTi independent of other clinicopathological parameters. CONCLUSIONS: Our results indicate that PEDF may serve as a promising novel modality for the treatment of bladder cancer, as it can inhibit not only angiogenesis but also EMT process of bladder cancer.

Distant metastasis is the primary cause of nasopharyngeal carcinoma (NPC) treatment failure while epithelial-mesenchymal transition (EMT) is the critical process of NPC invasion and metastasis. However, tumor-suppressor genes involved in the EMT and metastasis of NPC have not been explored clearly compared with the oncogenes. In the present study, the expression of pigment epithelium-derived factor (PEDF), a potent endogenous antitumor factor, was diminished in human NPC tissues and associated with clinicopathological and EMT features. The knockdown of PEDF induced EMT in lower metastatic NPC cell lines and overexpression of PEDF restored epithelial phenotype in higher metastatic NPC cell lines with typical EMT. The inhibition of PEDF mediated NPC cell spontaneous metastasis in vivo. LRP6/GSK3beta/beta-catenin signal pathway rather than AKT/GSK3beta pathway was involved in the effects of PEDF on EMT. The expression of PEDF was directly downregulated by elevated miR-320c in NPC. In conclusion, our findings indicate for the first time that PEDF functions as tumor-suppressor gene in the occurrence of EMT and metastasis in NPC. PEDF could serve as a promising candidate for NPC diagnosis, prognosis and treatment.

Pigment epithelium-derived factor (PEDF) has complex functions in tumor metastasis, but little is known about the roles of PEDF and its receptors in hepatocellular carcinoma (HCC). Here we found that high expression of PEDF is associated with shorter overall survival in HCC patients. Forced expression of PEDF enhanced HCC cell aggressive behavior in vitro and in vivo, whereas silencing PEDF expression reduced migration and invasion. Furthermore, PEDF expression led to changes in cell morphology and the expression of epithelial-mesenchymal transition (EMT)-related markers via ERK1/2 signaling pathway, including the upregulation of N-cadherin and slug, and the downregulation of E-cadherin in HCC cells. Our results further showed that PEDF could interact with laminin receptor (LR) and LR knockdown attenuated PEDF-induced migration, invasion and the change of EMT-related markers. More importantly, in clinical HCC specimens, we found that PEDF expression was correlated with subcellular localization of LR, and that high expression of PEDF and positive expression of LR predicted a poor prognosis. In conclusion, our results demonstrate a novel functional role of PEDF/LR axis in driving metastasis through ERK1/2-mediated EMT in HCC and provided a promising prognostic marker in HCC.