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

作者：Iida J^*; Wilhelmson KL; Price MA; Wilson CM; Pei DQ; Furcht LT; McCarthy JB

来源：Journal of Investigative Dermatology, 2004, 122(1): 167-176.

DOI：10.1046/j.0022-202X.2003.22114.x

• melanoma
• growth
• invasion

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.

• 出版日期2004-1