Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2013 Oct 13;13(1):98.
doi: 10.1186/1475-2867-13-98.

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

Guangyu Yao #  1 , Ping He #  2 , Lujia Chen  1 , Xiaolei Hu  1 , Fan Gu  1 , Changsheng Ye  1
Affiliations

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

Guangyu Yao et al. Cancer Cell Int. .

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.

PubMed Disclaimer

Figures

Figure 1
Figure 1
The correlation between MT1-MMP and VEGF-C expression in human breast cancer cells. (a) MT1-MMP and VEGF-C mRNA expression. (b) MT1-MMP and VEGF-C protein expression.
See this image and copyright information in PMC

References

    1. Genis L, Galvez BG, Gonzalo P, Arroyo AG. MT1-MMP: universal or particular player in angiogenesis? Cancer Metastasis Rev. 2006;13(1):77–86. doi: 10.1007/s10555-006-7891-z. - DOI - PubMed
    1. Itoh Y, Nagase H. Matrix metalloproteinases in cancer. Essays Biochem. 2002;13:21–36. - PubMed
    1. Zucker S, Pei D, Cao J, Lopez-Otin C. Membrane type-matrix metalloproteinases (MT-MMP) Curr Topics Dev Biol. 2003;13:1–74. - PubMed
    1. Sato H, Takino T, Okada Y, Cao J, Shinagawa A, Yamamoto E, Seiki M. A matrix metalloproteinase expressed on the surface of invasive tumour cells. Nature. 1994;13(6484):61–65. doi: 10.1038/370061a0. - DOI - PubMed
    1. Stetler-Stevenson WG, Liotta LA, Kleiner DE Jr. Extracellular matrix 6: role of matrix metalloproteinases in tumor invasion and metastasis. Faseb J. 1993;13(15):1434–1441. - PubMed

LinkOut - more resources