Increased aggressiveness of human prostate PC-3 tumor cells expressing cell surface localized membrane type-1 matrix metalloproteinase (MT1-MMP)

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

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

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 with the mutant form lacking the cytoplasmic tail (ΔC-MT1-MMP). Enhanced cell surface MT1-MMP was determined by fluorescence-activated cell sorting analysis and evidenced mechanistically by increased activation of proMMP-2 and invasion into type-I collagen gels. PC-3 cells overexpressing 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. ΔC-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 in other lipid raft structures, is a mechanism to localize this proteinase in contact with extracellular matrix and other pericellular proteins, the cleavage of which can facilitate prostate cancer cell invasion and metastasis.

Original languageEnglish (US)
Pages (from-to)259-274
Number of pages16
JournalJournal of Andrology
Volume30
Issue number3
DOIs
StatePublished - May 2009

Keywords

  • Cancer
  • Caveolae
  • MMP-14
  • Matrix metalloproteinase type-1
  • Tumor cell invasion
  • Type I collagen

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