Membrane type-1 matrix metalloproteinase promotes human melanoma invasion and growth

J Invest Dermatol. 2004 Jan;122(1):167-76. doi: 10.1046/j.0022-202X.2003.22114.x.

Abstract

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 entirely 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Biocompatible Materials
  • Cell Division
  • Cell Line, Tumor
  • Collagen
  • Collagen Type I
  • Collagen Type IV
  • Drug Combinations
  • Enzyme Precursors / genetics
  • Female
  • Fibrosarcoma
  • Gelatinases / genetics
  • Humans
  • Injections, Intradermal
  • Laminin
  • Matrix Metalloproteinase 14
  • Matrix Metalloproteinases, Membrane-Associated
  • Melanoma / pathology*
  • Metalloendopeptidases / genetics
  • Metalloendopeptidases / metabolism*
  • Mice
  • Mice, Inbred NOD
  • Neoplasm Invasiveness
  • Neoplasm Transplantation
  • Proteoglycans
  • Skin Neoplasms / pathology*
  • Transfection

Substances

  • Biocompatible Materials
  • Collagen Type I
  • Collagen Type IV
  • Drug Combinations
  • Enzyme Precursors
  • Laminin
  • Mmp14 protein, mouse
  • Proteoglycans
  • laminin 1
  • matrigel
  • Collagen
  • Gelatinases
  • Matrix Metalloproteinases, Membrane-Associated
  • Metalloendopeptidases
  • progelatinase
  • Matrix Metalloproteinase 14