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

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.

• Authors: Joji Iida, Krista L Wilhelmson, Matthew A Price, Christopher M Wilson, Duanqing Pei, Leo T Furcht, James B McCarthy
• Journal: The Journal of investigative dermatology (J Invest Dermatol) Vol. 122 Issue 1 Pg. 167-76 (Jan 2004) ISSN: 0022-202X [Print] United States
• PMID: 14962105 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• 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

Topics

• 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, metabolism)
• Mice
• Mice, Inbred NOD
• Neoplasm Invasiveness
• Neoplasm Transplantation
• Proteoglycans
• Skin Neoplasms (pathology)
• Transfection