Membrane Type-1 Matrix Metalloproteinase Promotes Human Melanoma Invasion and Growth

Joji Iida, Krista L. Wilhelmson, Matthew A. Price, Christopher M. Wilson, Duanqing Pei, Leo T. Furcht, James B. McCarthy

Research output: Contribution to journalArticle

59 Scopus citations


Membrane type-I metalloproteinase (MT1-MMP) is a transmembrane metalloproteinase that is critical for tumor cell invasion. MT1-MMP can degrade extracellular matrix (ECM) proteins directly and/or indirectly by activating soluble MMPs such as pro-MMP-2. Although MT1-MMP is upregulated in malignant melanoma, the biological consequences of elevated MT1-MMP expression for tumor progression are not enirely understood. In the current study, we have utilized the Bowes melanoma line for evaluating MT1-MMP in invasion and growth. Our studies extend the earlier observations to demonstrate that MT1-MMP expression in Bowes melanoma cells promotes selective invasion into matrigel but not matrices consisting of type-I collagen. Furthermore, MT1-MMP expressing melanoma cells exhibit increased migration in response to laminin 1 but not to type-I or type-IV collagen. MT1-MMP expression results in enhanced 3 dimensional growth in agarose gels and in long-term cultures within matrigel. The hydroxymate inhibitor BB94 inhibits MT1-MMP enhanced invasion and growth in 3 dimensional culture systems, but had no effect on increased motility. We demonstrated that MT1-MMP expression significantly facilitated tumorigenicity and growth by intradermal injection. The results suggest a more general role for elevated MT1-MMP in promoting both the selective invasion and increased growth of malignant melanoma in vivo.

Original languageEnglish (US)
Pages (from-to)167-176
Number of pages10
JournalJournal of Investigative Dermatology
Issue number1
StatePublished - Jan 2004


  • Growth
  • Invasion
  • Melanoma

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