title: MT1-MMP in breast cancer: induction of VEGF-C correlates with metastasis and poor prognosis.
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 (n = 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.
authors.affiliation: Breast Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China.
authors.forename: Guangyu
authors.initials: G
authors.lastname: Yao
authors.affiliation: Department of Pathology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, Guangdong Province, China.
authors.forename: Ping
authors.initials: P
authors.lastname: He
authors.affiliation: Breast Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China.
authors.forename: Lujia
authors.initials: L
authors.lastname: Chen
authors.affiliation: Breast Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Hu
authors.affiliation: Breast Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Gu
authors.affiliation: Breast Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China.
authors.forename: Changsheng
authors.initials: C
authors.lastname: Ye