Matrix metalloproteinases in human melanoma

Cutaneous melanoma is a highly invasive and metastatic tumor. Degradation o f basement membranes and extracellular matrix is an essential step in melan oma cell migration, invasion, and metastasis formation. Matrix metalloprote inases and their tissue inhibitors play a crucial role in these complex mul tistep processes. Melanoma cells may express a number of matrix metalloprot einase family members (MMP-1, MMP-2, MMP-9, MMP-13, and MT1-MMP) as well as their tissue inhibitors (TIMP-1, TIMP-2, and TIMP-3). Numerous studies hav e examined matrix metalloproteinases, their tissue inhibitors, and the mole cules that regulate their expression and/or activation in melanoma cell lin es in vitro and in vivo, and in human melanocytic lesions. Recent results h ave indicated that adhesion molecutes such as CD44 and integrin alpha(v)bet a(3) are involved in positioning activated matrix metalloproteinase molecul es on the cell surface of invasive tumor cells. In this review we evaluate these novel aspects of the role of matrix metalloproteinases and their tiss ue inhibitors in melanoma progression. We conclude that the balance between levels of activated matrix metalloproteinases and expression levels of the ir tissue inhibitors, and the coexpression of activated matrix metalloprote inases and adhesion molecules are important factors in determining melanoma cell invasion, tumor growth, and metastasis formation.