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PGF

epithelial-mesenchymal transition (EMT) plays an important role in cancer invasion and metastasis by enabling cancer cells to depart from the primary tumor, invade surrounding tissue and disseminate to distant organs. The existence and function of EMT in cervical cancer is poorly understood. Placental growth factor (PLGF) has been shown to associate with EMT in various cancers. However, whether PLGF is involved in EMT in cervical cancer remains unclear. Thus the present study examined the relationship between PLGF expression and EMT-related proteins in 110 cervical lesions samples. We detected that PLGF was expressed in 61.8% cervical lesion sections. In addition, PLGF expression is positively correlated with low expression level of E-cadherin and high expression level of vimentin. Serum samples and cervical lavage samples were collected from patients with pre-invasive and invasive lesion of uterine cervix or normal control group, the PLGF levels were determined by enzyme-linked immunosorbent assay (ELISA). We found that a significantly high level of PLGF could be detected both in serum and vaginal lavage compared with normal women group, and there is no significant difference between serum and lavage in PLGF level. In addition, whatever in lavage or in serum, the PLGF level in stage I and II was significantly higher than it in CINIII or cancer in situ. However, there is no significant difference between the stage I and stage II; we also found that exogenous PLGF promotes molecular changes of epithelial-mesenchymal transition (EMT) in siha cells. In addition, application of a specific EKR1/2 inhibitor could reverse the effects of PLGF. These findings suggested that PLGF could regulate the expression of EMT-related proteins and promote migration of siha cells through ERK/MAPK signaling pathway. Therapies that targets PLGF/Flt-1/ERK/MAPK signaling pathway may be beneficial in treatment of cervical cancer.

Gallbladder cancer (GBC) is the most common malignant tumor of the biliary tract system. epithelial-mesenchymal transition (EMT) plays a vital role in the process of tumor metastasis. mesenchymal-like cells can serve as a source of cancer stem cells, which can confer the EMT phenotype. Placental growth factor (PLGF) belongs to the vascular endothelial growth factor family and plays a vital role in cancer. However, the underlying molecular mechanisms about the influence of PLGF on EMT in GBC remain unknown. Here we show that PLGF expression levels were higher in GBC tissues than in normal adjacent tissues and were associated with poor prognosis in GBC patients. Exogenous PLGF enhanced the migration, invasion, and tumorsphere formation of GBC cells. Conversely, knockdown of PLGF decreased the aggressive phenotype of GBC cells. Mechanistically, exogenous PLGF upregulated microRNA-19a (miR-19a) expression through the activation of c-MYC. Moreover, Spearman's correlation analysis showed a positive pairwise correlation among PLGF, c-MYC, and miR-19a expression in GBC tissues. Taken together, these results suggest that PLGF promotes EMT and tumorsphere formation through inducing miR-19a expression by upregulating c-MYC. Thus, PLGF could be a promising molecular therapeutic target for GBC.CI - (c) 2018 The Authors. cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese cancer Association.

Purpose: To investigate the role of placental growth factor (PGF) in the epithelial-mesenchymal transition (EMT) of ARPE-19 cells under hypoxia, and whether the NF-kappaB signaling pathway is involved in this process. Methods: ARPE-19 cells were treated in five groups: a control group, hypoxia group, PGF group, hypoxia+PGF group, and NF-kappaB-blocked group. A chemical hypoxia model was established in the ARPE-19 cells by adding CoCl2 to the culture medium. The morphological changes after treatment were observed. The proliferation rates were measured with 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The migration abilities were measured with scratch assay. The EMT biomarkers were measured with quantitative real-time PCR (qRT-PCR), western blotting, and immunofluorescence. The relative protein expression of components of the NF-kappaB signaling pathway was measured with western blotting and immunofluorescence. Results: Cells treated with PGF under hypoxia exhibited morphological changes consistent with the transition from an epithelial to a mesenchymal phenotype. In the ARPE-19 cells, exogenous PGF under hypoxia increased the proliferation rate compared to the rate under hypoxia alone (p<0.05) and increased the migration rate (p<0.05). Treatment of hypoxia-exposed cells with PGF caused decreased expression of the epithelial biomarkers E-cadherin and ZO-1 (both p<0.05) and increased expression of the mesenchymal marker alpha-SMA (p<0.05) by enhancing the phosphorylation of NF-kappaB p65 of the total protein, promoting the translocation of p65 to the nucleus, and inducing the degradation of IkappaB-alpha (a negative regulator of the NF-kappaB pathway) in the ARPE-19 cells. Additionally, the effect of PGF-induced EMT in the ARPE-19 cells under hypoxia was counteracted with BAY 11-7082 (a selective NF-kappaB inhibitor). Conclusions: Exogenous PGF promotes EMT-like changes in ARPE-19 cells under hypoxia by activating the NF-kappaB signaling pathway. The study results suggest that PGF may play a role in scar formation in neovascular age-related macular degeneration (AMD) and that the inhibition of PGF may be a promising target for the prevention and treatment of AMD.