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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.

Abstract

AIMS:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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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