Inhibitory effects of pigment epithelium-derived factor on epithelial-mesenchymal transition migration and invasion of breast cancer

摘要

Objective: Pigment epithelium-derived factor (PEDF) is a ubiquitously expressed secreted protein that suppresses tumor growth and metastasis by targeting tumor cells and their microenvironment. However, the exact mechanism of PEDF on breast cancer metastasis including liver and lung metastasis remains unclear. Epithelial-mesenchymal transition (EMT) is a pivotal event in the progression of cancer towards metastasis. In the present report, we investigated whether PEDF inhibits breast cancer metastasis through epithelial-mesenchymal transition and elucidate the association of PEDF expression and EMT in vitro. Methods: Our analyses were performed on 102 tissue samples of patients with primary BC and a set of 20 control samples of healthy women, respectively. Lentiviruses were used to stably express PEDF in SkBr3 breast cancer cell line to determine EMT factors changes of invasion ability following PEDF re-expression. PEDF and EMT factors protein levels were measured in SkBr3 breast cancer cell line using western blot analyses. Results: We show that the important inhibitor of angiogenesis, pigment epithelium-derived factor expression positively correlatedwith lymph node-positive tumor status and tumor size, low expression level of vimentin, and high expression levels of membranous E-cadherin. In addition, we found that PEDF activation suppressed migration and invasion in SKBR3 (luminal) cellsand led to morphologic and molecular changes of epithelial-mesenchymal transition (EMT). Loss of PEDF promotesmesenchymal phenotype, whereas PEDF was shown to effectively promotes epithelial phenotyperesulted ininhibited the growthof endocrine-resistant SkBr3 breast cancer cells invitro. Finally, western blot examination of PEDF/siRNA-expressing tumor showed down-regulation of E-cadherin and up-regulation of vimentin. Conclusions: These findings suggest that PEDF is directly linked to the mechanisms that suppress metastasis of breast cancer through regulating epithelial-mesenchymal transition. In the future, contribute to evaluate the efficacy of PEDF targetedtherapy early during the course of the disease, may be beneficial in the treatment of breast cancer patients.