Abstract
Phosphatase of regenerating liver-3 (PRL-3) has been proposed to promote the invasion of tumor cells to metastasis sites. However, the effect of PRL-3 on spontaneous metastasis has not been clearly demonstrated, and whether PRL-3 could become a new therapeutic target in malignant tumor is still unknown. In this study, we used PRL-3 siRNA as a molecular medicine to specifically reduce the expression of PRL-3 in B16-BL6 cells, a highly metastatic melanoma cell line. In vitro, PRL-3 siRNA significantly inhibited cell adhesion and migration, but had no effect on cell proliferation. In the spontaneous metastatic tumor model in vivo, PRL-3 siRNA treatment remarkably inhibited the proliferation of primary tumor, prevented tumor cells from invading the draining lymph nodes, and prolonged the life span of mice. Therefore, our results indicate that PRL-3 plays a critical role in promoting the whole process of spontaneous metastasis and tumor growth initiation, and that inhibiting PRL-3 will improve malignant tumor therapy.
Highlights
Metastasis is a leading reason for cancer mortality and involves a complex, multistep progress by which tumor cells disseminate to distant sites to establish discontinuous secondary colonies [1,2]
Our previous study indicated that highly metastatic B16-BL6 melanoma cells express more elevated Phosphatase of regenerating liver-3 (PRL-3) than less metastatic B16 cells [10]
phosphatase of regenerating liver (PRL)-1 and PRL-2, which share at least 75% homologous protein sequence with PRL-3 [22,23], were detected in B16-BL6 cells, PRL-3 siRNA treatment only reduced the endogenous expression of PRL-3 in B16-BL6 cells, with no influence on the expression of PRL-1 and PRL-2 (Figure 1C)
Summary
Metastasis is a leading reason for cancer mortality and involves a complex, multistep progress by which tumor cells disseminate to distant sites to establish discontinuous secondary colonies [1,2]. The PRLs (PRL-1, -2, and -3) are relatively small proteins of ~22 kDa with at least 75% amino acid sequence similarity, containing the protein tyrosine phosphatase (PTP) active domain (CX5R) and a C-terminal CAAX sequence for prenylation [6]. Among these PRLs, PRL-1 is overexpressed in breast, prostate, ovarian, and pancreatic cancers, while PRL-2 can lead to epithelial cell transformation and forms tumors in nude mice [6,7,8]. Overexpression of PRL-3 in mouse low-metastatic B16 cells and CHO cells promotes their migration and invasion in vitro, and enhances their metastatic ability to lung and liver in experimental passive metastatic models, which are es-
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
