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Updated: Aug 11, 2026

Tissue Engineering of Tumor Stromal Microenvironment with Application to Cancer Cell Invasion
Published on: March 18, 2014
Membrane type-1 matrix metalloproteinase promotes human melanoma invasion and growth
Joji Iida1, Krista L Wilhelmson, Matthew A Price
1Department of Laboratory Medicine and Pathology, and University of Minnesota Cancer Center, University of Minnesota, Minneapolis, Minnesota 55455, USA. iidax002@tc.umn.edu
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.
Insights
Elevated membrane type-I metalloproteinase (MT1-MMP) expression in melanoma cells promotes selective invasion and enhances tumor growth. Inhibition of MT1-MMP blocks invasion but not motility, suggesting a key role in melanoma progression.
Area of Science:
- Biochemistry
- Molecular Biology
- Cancer Research
Background:
- Membrane type-I metalloproteinase (MT1-MMP) is crucial for tumor cell invasion and extracellular matrix degradation.
- MT1-MMP is upregulated in malignant melanoma, but its precise role in tumor progression is not fully understood.
Purpose of the Study:
- To investigate the biological consequences of elevated MT1-MMP expression in melanoma cells.
- To evaluate the role of MT1-MMP in melanoma invasion, migration, growth, and tumorigenicity.
Main Methods:
- Utilized the Bowes melanoma cell line to assess MT1-MMP function.
- Examined invasion and migration across different extracellular matrix components (matrigel, type-I collagen, laminin 1, type-IV collagen).
- Assessed 3D growth in agarose gels and matrigel, and tumorigenicity via intradermal injection. Evaluated the effect of the inhibitor BB94.
Main Results:
- MT1-MMP expression promoted selective invasion into matrigel but not type-I collagen.
- Melanoma cells expressing MT1-MMP showed increased migration towards laminin 1.
- MT1-MMP enhanced 3D growth and tumorigenicity in vivo. BB94 inhibited MT1-MMP-driven invasion and growth but not motility.
Conclusions:
- Elevated MT1-MMP expression in melanoma facilitates selective invasion and enhances tumor growth.
- MT1-MMP plays a significant role in promoting malignant melanoma progression in vivo.
- Targeting MT1-MMP may offer therapeutic strategies for melanoma treatment.
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