MT1-MMP prevents growth inhibition by three dimensional fibronectin matrix.

The extracellular microenvironment plays a key role in regulation of cellular functions and growth control. We show here that membrane-type 1 matrix metalloproteinase (MT1-MMP) acts as a growth promoter in confluent culture. When MT1-MMP was silenced in HT1080 fibrosarcoma cells, cells created three dimensional (3D) fibronectin matrix in a confluent culture, and growth of cells embedded within it was retarded. Formation of 3D fibronectin matrix initiated by MT1-MMP silencing was impeded by knockdown of either FN or integrin β₁, which resulted in restoration of cell growth. When cells in 3D fibronectin matrix were treated with integrin β₁ inhibitory antibody, cells underwent S phase entry. These results suggest that MT1-MMP prevents growth suppression by 3D fibronectin matrix, which is mediated through integrin β₁.