Protein tyrosine phosphatase PRL-3 in malignant cells and endothelial cells: expression and function

Rouleau, Cecile; Roy, Amélie; Martin, Thomas N.; Dufault, Michael R.; Boutin, Paula; Liu, Dapei; Zhang, Mindy; Puorro-Radzwill, Kristin; Rulli, Lori; Reczek, Dave; Bagley, Rebecca G.; Byrne, Annette T.; Weber, William; Roberts, Bruce; Klinger, Katherine W.; Brondyk, William; Nacht, Mariana; Madden, Steve; Burrier, Robert E.; Shankara, Srinivas; Teicher, Beverly A.

doi:10.1158/1535-7163.mct-05-0289

Cited by 58 publications

(61 citation statements)

References 39 publications

(22 reference statements)

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“…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). PRL-3 plays a more notable role in metastatic cancer cells.…”

Section: Introductionmentioning

confidence: 99%

PRL-3 siRNA Inhibits the Metastasis of B16-BL6 Mouse Melanoma Cells In Vitro and In Vivo

Feng

Sheng

et al. 2007

Mol Med

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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.

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Section: Introductionmentioning

confidence: 99%

PRL-3 siRNA Inhibits the Metastasis of B16-BL6 Mouse Melanoma Cells In Vitro and In Vivo

Feng

Sheng

et al. 2007

Mol Med

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“…Moreover, we observed a higher incidence of subsequent distant metastases in patients with PRL-3 overexpressing breast carcinomas. In addition, Rouleau et al (2006) could demonstrate, that PRL-3 actively promotes invasiveness of MCF-7 cells in vitro. In summary, overexpression of PRL-3 might facilitate tumour cells to invade into lymphatics or vasculature, and therefore being a prerequisite for development of local lymph node and distant metastases.…”

Section: Discussionmentioning

confidence: 93%

“…Results of these studies suggest that an excess of PRL-3 may play a key role in the acquisition of metastatic potential of tumour cells. To date, with respect to breast cancer, there are only data on PRL-3 expression in several breast cancer cell lines available, as recently reported by Rouleau et al (2006).…”

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confidence: 96%

Expression and prognostic impact of the protein tyrosine phosphatases PRL-1, PRL-2, and PRL-3 in breast cancer

et al. 2006

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The aim of this study was to investigate the expression of the protein tyrosine phosphatases (PTP) PRL-1, PRL-2, and PRL-3 in human breast cancer and to evaluate its clinical and prognostic significance. PRL-PTP mRNA expression was examined in malignant (n ¼ 7) and nonmalignant (n ¼ 7) cryoconserved breast tissue samples as well as in eight breast cancer cell lines by RT -PCR. Furthermore, protein expression of PRL-3 was analysed semiquantitatively by immunohistochemistry in ductal breast carcinoma in situ (n ¼ 135) and invasive breast cancer (n ¼ 147) by use of tissue microarray technology (TMA). In 24 lymph node-positive patients we selected the corresponding lymph node metastases for analysis of PRL-3 expression, and a validation set (n ¼ 99) of invasive breast cancer samples was examined. Staining results were correlated with clinicopathological parameters and long-term follow-up. PRL-3 mRNA expression was significantly higher in malignant compared to benign breast tissue. For PRL-1 and PRL-2 expression no significant differences were observed. Staining of TMAs showed PRL-3 expression in 85.9% ductal carcinoma in situ and 75.5% invasive breast carcinomas. Analysis of survival parameters revealed a shorter disease-free survival (DFS) in patients with PRL-3-positive carcinomas, and in particular a significantly shorter DFS in nodal-positive patients with PRL-3 overexpressing tumours as compared to PRL-3-negative breast carcinomas (6677 months (95% CI, 52 -80) vs 9779 months (95% CI, 79 -115); P ¼ 0.032). Moreover, we found a more frequent expression of PRL-3 in lymph node metastases as compared to the primary tumours (91.7 vs 66.7%; P ¼ 0.033). Our results suggest that PRL-3 might serve as a novel prognostic factor in breast cancer, which may help to predict an adverse disease outcome.

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“…DLD-1, SW480, MCF7 and A2780 cells were used as expression controls, where DLD-1 cells and the other cells have been reported as weak and intense expression of PRL-3, respectively. 17,18 On Q-RT-PCR, 5 ESCC cell lines (TE6, TE8, TE10, TE11 and TE14 cells) exhibited a strong expression of the PRL-3 mRNA (more than 5-fold compared to DLD-1 cells, Fig. 1a left panel).…”

Section: Prl-3 Expression and Gene Amplification In Escc Cell Linesmentioning

confidence: 99%

Phosphatase of regenerating liver‐3 as a convergent therapeutic target for lymph node metastasis in esophageal squamous cell carcinoma

Ooki

Yamashita

Kikuchi

et al. 2010

Intl Journal of Cancer

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Phosphatase of regenerating liver-3 (PRL-3) is a molecule associated with metastasis in a diverse of cancers, which, however, remains largely unknown in esophageal squamous cell carcinoma (ESCC). We examined both the clinical significance of PRL-3 expression and its biological roles, and assessed possibilities as a therapeutic target in ESCC. PRL-3 expression was found in 78% (69 of 88) of the primary ESCC on immunohistochemistry; it was the strong independent predictor for lymph node metastasis (LNM) on a multivariate logistic regression model (p 5 0.0014, relative risk 515.20). Additionally, gene amplification was found in 3 (7.9%) of the 38 primary tumors with PRL-3 overexpression by fluorescence in situ hybridization, but in none of the 19 tumors without it. PRL-3 small interfering RNA robustly repressed cell proliferation, anchorageindependent colony formation and invasion and augmented 5-FU-induced apoptosis in all the tested ESCC cell lines with PRL-3 overexpression, irrespective of its gene amplification status. PRL-3 inhibitor (1-4-bromo-2-benzylidene rhodanine) also suppressed such metastatic properties in the cell lines with PRL-3 overexpression, but not with its low expression. Inverse effects were observed by PRL-3 forced expression. Collectively, PRL-3 overexpression is a frequent event associated with LNM and plays a causative role in promoting cancer progression. Moreover, the expression status may be a landmark to select patients with benefit from PRL-3-targeted therapy. Thus, PRL-3 could be a convergent therapeutic target against ESCC with LNM.

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Protein tyrosine phosphatase PRL-3 in malignant cells and endothelial cells: expression and function

Cited by 58 publications

References 39 publications

PRL-3 siRNA Inhibits the Metastasis of B16-BL6 Mouse Melanoma Cells In Vitro and In Vivo

PRL-3 siRNA Inhibits the Metastasis of B16-BL6 Mouse Melanoma Cells In Vitro and In Vivo

Expression and prognostic impact of the protein tyrosine phosphatases PRL-1, PRL-2, and PRL-3 in breast cancer

Phosphatase of regenerating liver‐3 as a convergent therapeutic target for lymph node metastasis in esophageal squamous cell carcinoma

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