Matrix Metalloproteinase-9 Promotes Membrane Protrusive Activity in Ovarian Cancer Cells

Matrix Metalloproteinase-9 (MMP9) is an extracellular endopeptidase associated with ovarian cancer development and progression. To further understand MMP9 contributions to metastatic behavior of an established ovarian cancer cell line (OVCA433), we utilized CRISPR to generate seven cell clones null for MMP9 expression. Analysis of the pooled clones revealed MMP9-null cells exhibited identical phenotype and growth compared to parental OVCA 433 cells. Cell adhesion and transwell migration towards type I collagen was also not impacted by MMP9 loss. MMP9-null cells were significantly delayed, however, in EGF-driven non-directional filamentous actin-based membrane protrusions on a variety of matrix substrates. Further, over or re-expression of MMP9 in OVCA433 or MMP9-null cells, respectively, was sufficient to drive both lamellipodial and filopodial membrane protrusions on glass. These results indicate MMP9 directly contributes to ovarian cancer cell protrusive activity. © FASEB.