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Open Access Highly Accessed Primary research

MT1-MMP in breast cancer: induction of VEGF-C correlates with metastasis and poor prognosis

Guangyu Yao1, Ping He2, Lujia Chen1, Xiaolei Hu1, Fan Gu1 and Changsheng Ye1*

Author Affiliations

1 Breast Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China

2 Department of Pathology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, Guangdong Province, China

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Cancer Cell International 2013, 13:98  doi:10.1186/1475-2867-13-98

Published: 13 October 2013

Abstract

Background

Recent evidence suggests that vascular endothelial growth factor-C (VEGF-C)- dependent tumour production promotes lymphangiogenesis, while membrane-type matrix 1 metalloproteinase (MT1-MMP) is involved in the critical steps leading to carcinogenesis. However, the role of MT1-MMP in lymphangiogenesis and lymphatic metastasis remains poorly understood. In the present study, we investigated the relationship between MT1-MMP and VEGF-C in human breast cancer and correlated MT1-MMP and VEGF-C expression with lymphangiogenesis and prognosis.

Methods

MT1-MMP and VEGF-C levels were compared in five breast carcinoma cell lines. We used a membrane invasion assay to assess the effect of MT1-MMP and VEGF-C expression, as well as anti-MT1-MMP and VEGF-C antibodies, on cancer cell invasion. We further assessed MT1-MMP and VEGF-C immunoreactivity and lymph vessels in a cohort of human breast cancer specimens (nā€‰=ā€‰106) and associated MT1-MMP and VEGF-C expression with clinicopathological parameters, such as lymphatic vessel density (LVD), and patient prognosis.

Results

MT1-MMP and VEGF-C expression differed among the five breast cancer cell lines and MT1-MMP and VEGF-C expression were correlated with tumour cell invasion. VEGF-C mRNA expression levels and invasive activity of MDA-MB-231 cells was inhibited by an anti-MT1-MMP antibody in a concentration-dependent manner. A significant correlation was found between the expression of MT1-MMP and VEGF-C in breast cancer patient samples and elevated MT1-MMP and VEGF-C expression was associated with higher LVD, lymph node metastasis, cancer stage, and a decline in overall survival rates.

Conclusions

Our data demonstrate that MT1-MMP expression is closely correlated with VEGF-C expression, and that MT1-MMP promotes lymphangiogenesis by up-regulating VEGF-C expression in human breast cancer. Thus, elevated MT1-MMP may serve as a significant prognostic factor in breast cancer.

Keywords:
Membrane-type matrix 1 metalloproteinases; Vascular endothelial growth factor-C; Lymphangiogenesis; Metastasis; Breast cancer