Mesothelin Promotes Invasion and Metastasis in Breast Cancer Cells

Abstract

OBJECTIVE: The presence of mesothelin (encoded by the mesothelin [MSLN] gene) in breast cancer is associated with tumour infiltration of the lymph node. This study evaluated whether MSLN overexpression promotes breast cancer cell invasiveness and metastasis. METHODS: This study evaluated the effects of overexpression of MSLN on extracellular signal-regulated kinase (ERK1/2) and matrix metalloproteinase (MMP)-9 levels, and the invasiveness and angiogenesis of the breast cancer cell line MCF-7 in vitro, and on MCF-7-derived tumour development in vivo. RESULTS: MSLN overexpression significantly increased ERK1/2 and MMP9 protein levels and activity, and the invasive and angiogenic capability of MCF-7 cells, in vitro. Inhibition of ERK1/2 suppressed MMP-9 and the invasive and angiogenic capability of MSLN overexpressing MCF-7 cells. MSLN overexpression also increased MCF-7-derived tumour metastasis in vivo. CONCLUSION: MSLN overexpression promoted the invasive potential of MCF-7 cells through ERK1/2-dependent upregulation of MMP-9; this association may have contributed to metastasis of MCF-7 cells in vivo. Mesothelin may be a useful biomarker for cancer progression and a novel therapeutic or chemopreventive target in human breast cancer.