Journal of Andrology Testis Workshop 2009
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Published-Ahead-of-Print January 8, 2009, DOI:10.2164/jandrol.108.006494

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Increased Aggressiveness of Human Prostate PC-3 Tumor Cells Expressing Cell Surface Localized Membrane Type-1 Matrix Metalloproteinase (MT1-MMP)

Xing Wang , Michael Wilson *, Joel W. Slaton , Akhouri A. Sinha , Stephen W.L. Ewing , and Duanqing Pei

* To whom correspondence should be addressed. E-mail: wilso042{at}umn.edu.

Membrane type-1 matrix metalloproteinase (MT1-MMP) is a multidomain transmembrane endopeptidase with a major role in physiological and pathological processes through proteolysis of extracellular matrix and other pericellular proteins. We examined cell surface function of MT1-MMP in PC-3 human prostate tumor cells selected for metastasis in nude mice (PC-3-LN4), or transfected with the full length wild type (WT) MT1-MMP or mutant form lacking the cytoplasmic tail ({Delta}C-MT1-MMP). Enhanced cell surface MT1-MMP was determined by FACS analysis and evidenced mechanistically by increased activation of proMMP-2 and invasion into type-I collagen gels. PC-3 cells over-expressing MT1-MMP grew faster than mock-transfected control cells subcutaneously in nude mice. MT1-MMP localized in caveolae as judged by immunofluorescence microscopy and sucrose-gradient, detergent-resistant cell fractionation. {Delta}C-MT1-MMP was strongly associated with caveolae, whereas the WT form was present in both caveolae and noncaveolae fractions. The role of plasma membrane MT1-MMP was supported by localization of MT1-MMP by immunofluorescence microscopy at the cell surface of tumor cells in primary prostate cancers. Increased plasma membrane localization of MT1-MMP, either in caveolae or other lipid raft structures, is a mechanism to localize this proteinase in contact with extracellular matrix and other pericellular poteins, the cleavage of which can facilitate prostate cancer cell invasion and metastasis.


Key words: Prostate • cancer • caveolae • invasion




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H. Yamaguchi, Y. Takeo, S. Yoshida, Z. Kouchi, Y. Nakamura, and K. Fukami
Lipid Rafts and Caveolin-1 Are Required for Invadopodia Formation and Extracellular Matrix Degradation by Human Breast Cancer Cells
Cancer Res., November 15, 2009; 69(22): 8594 - 8602.
[Abstract] [Full Text] [PDF]


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