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Significance Matrix metalloproteinases (MMPs) are a family of enzymes that enable cell-mediated remodeling of the local environment. Because of their ability to degrade the extracellular matrix, MMPs are an important component of the metastatic cascade. However, the effect of cancer drug treatment on MMP activity is not well-established. This study reveals that treatment with a clinically relevant BRAF protein kinase inhibitor (PLX4032) correlates with increases in melanoma MMP activity in 3D culture, which consequently leads to increased cell migration. Although PLX4032 initially causes significant tumor shrinkage, patients typically relapse due to metastatic lesions. This work may contribute to our understanding of how initially promising therapeutics ultimately lead to poor patient outcome through drug-induced effects on MMP activity and cell motility.

Multifunctional bioscaffolds for 3D culture of melanoma cells reveal increased MMP activity and migration with BRAF kinase inhibition