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Pathology. 2009 Feb;41(2):118-26. doi: 10.1080/00313020802579268.

PRL-3 facilitates angiogenesis and metastasis by increasing ERK phosphorylation and up-regulating the levels and activities of Rho-A/C in lung cancer.

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  • 1Department of Pathology, College of Basic Medical Sciences, China Medical University and First Affiliated Hospital of China Medical University, Shenyang, China.



The aim of this study was to investigate the mechanism of PRL-3 in inducing angiogenesis and lymphangiogenesis to promote distant and lymph node metastasis in human lung cancer tissues and cells.


We investigated the expression of PRL-3, VEGF, and VEGF-C from 94 patients with non-small cell lung cancer (NSCLC) using immunohistochemical staining. The relationship between PRL-3 expression and microvessel density (MVD), lymphatic vessel density (LVD), clinicopathological factors, and surgical treatment outcome was also studied. Following this, we studied the effect on A549 by blocking PRL-3.


PRL-3 expression in NSCLC was high, and this over-expression is correlated with advanced clinical stage (p = 0.019), distant metastasis (p = 0.001), lymph node metastasis (p = 0.001), and poor post-operative survival. PRL-3 over-expression was associated with vascular endothelial growth factor (VEGF; p = 0.000) and VEGF-C (p = 0.008) expressions, MVD and LVD (p = 0.000 and p = 0.000). Blocking PRL-3 expression in A549 cell resulted in decreased cellular proliferative, migratory, and invasive abilities, and VEGF, VEGF-C, pERK, Rho-A, and Rho-C expression was inhibited. Following inhibition of either Rho or pERK, VEGF expression was down-regulated.


PRL-3 induces microvascular and lymphatic vessel formation by facilitating VEGF and VEGF-C expression in lung cancer tissues, thus promoting distant and lymph node metastasis of lung cancer. PRL-3 up-regulates pERK and Rho expression and activity, facilitating VEGF expression, and accelerating angiogenesis and distant metastasis. How to regulate VEGF-C expression needs to be further studied.

[PubMed - indexed for MEDLINE]
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