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Thromb Haemost 2005; 93(04): 770-778
DOI: 10.1160/TH04-08-0555
Cellular Proteolysis and Oncology
Schattauer GmbH

Membrane type 1-matrix metalloproteinase promotes human prostate cancer invasion and metastasis

Jian Cao
1   Department of Medicine, State University of New York, Stony Brook, New York, USA
,
Christian Chiarelli
1   Department of Medicine, State University of New York, Stony Brook, New York, USA
,
Pallavi Kozarekar
1   Department of Medicine, State University of New York, Stony Brook, New York, USA
,
Howard L. Adler
2   Department of Urology, Schools of Medicine, State University of New York, Stony Brook, New York, USA
› Author AffiliationsPartly presented at the Second Chianti Meeting on Proteases held in Tuscany, Italy, from May 16–20, 2004
Further Information

Publication History

Received 30 August 2004

Accepted after resubmission 06 January 2005

Publication Date:
14 December 2017 (online)

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Summary

Development of metastases requires cancer cells to breach underlying basement membrane, migrate through interstitial stroma and gain access to blood or lymphatic vessels. Membrane type 1-matrix metalloproteinase (MT1-MMP) has been linked with these processes. Expression of MT1-MMP in human prostate cancer correlates with the stage of this disseminated disease. The mechanism underlying this observation, however, still remains to be understood. To study the role of MT1-MMP in prostate cancer dissemination, endogenous and recombinant MT1-MMP expressed in human prostate cancer cell lines (DU-145 and LNCaP) were examined. Using FITC-labeled Ma-trigel, a soluble basement membrane extract coated coverslips, LNCaP cells stably expressing a chimera of MT1-MMP and Green Fluorescent Protein (MT1-GFP) degraded Matrigel and readily migrated over degraded substrates. The degradation of Matrigel by LNCaP cells expressing MT1-GFP was sensitive to MMP inhibitors, CT-1746 and TIMP-2, but not TIMP-1. Cell migration was dramatically enhanced by expression of MT1-MMP. By employing surgical orthotopic implantation of LNCaP cells stably expressing MT1-GFP into the prostate gland of immunodeficient mice, we demonstrated that MT1-MMP promotes lymph node and lung metastasis of prostate cancer cells. Together, these results emphasize the pivotal role of MT1-MMP in prostate cancer dissemination and confirm that MT1-MMP is a suitable target to prevent cancer metastasis.

Keywords

MT1-MMP - cell migration - invasion - metastasis - prostate cancer
 

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