Placenta growth factor promotes migration through regulating epithelial-mesenchymal transition-related protein expression in cervical cancer

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.