Matrix metalloproteinase-9 regulates cell adhesion and membrane protrusive activity of ovarian cancer cells.

Matrix metalloproteinase-9 (MMP9), an extracellular endopeptidase, is upregulated by Epidermal Growth Factor (EGF) signaling and associated with ovarian epithelial cancer progression. To further understand the contribution of MMP9 to EGF-stimulated metastatic behavior, we created MMP9-null cells (M9-KO) from an ovarian cancer cell line. This model showed MMP9 loss did not block EGF-driven E-cadherin dissolution and associated epithelial-to-mesenchymal transition. However, MMP9-null cells exhibited delayed and reduced EGF-driven actin-based membrane protrusions, with transient re-expression of MMP9 sufficient to drive both lamellipodial and filopodial membrane protrusions. Finally, M9-KO cells exhibited a reduction of adhesion to extracellular matrices, which was significantly recovered by stable re-expression of MMP9. Together, these results provide direct evidence that MMP9 mediates EGF-driven membrane protrusions and promotes ovarian cancer cell adhesion to mesothelial extracellular matrices. Impact statement This work provides direct evidence that MMP9 mediates EGF-driven membrane protrusions and promotes ovarian cancer cell adhesion to mesothelial extracellular matrices.