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- Title
Membrane Type-1 Matrix Metalloproteinase Promotes Human Melanoma Invasion and Growth.
- Authors
Iida, Joji; Wilhelmson, Krista L.; Price, Matthew A.; Wilson, Christopher M.; Pei, Duanqing; Furcht, Leo T.; McCarthy, James B.
- 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 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.
- Subjects
METALLOPROTEINASES; MELANOMA; GENE expression; CANCER invasiveness; TUMORS; DERMATOLOGY
- Publication
Journal of Investigative Dermatology, 2004, Vol 122, Issue 1, p167
- ISSN
0022-202X
- Publication type
Article
- DOI
10.1046/j.0022-202X.2003.22114.x