Effect of MT1-MMP Deficiency and Overexpression in Corneal Keratocytes on Vascular Endothelial Cell Migration and Proliferation

PURPOSE: To determine the effect of keratocyte-derived MT1-MMP on calf pulmonary artery endothelial cell (CPAE) proliferation and migration. METHODS: Keratocyte lines were generated from MT1-MMP knockout (KO) and wild type (WT) mice. WT keratocytes were transfected with WT or mutant MT1-MMP DNAs (DeltaTC or E240A). The effect of keratocyte-conditioned media on CPAE proliferation and migration was assayed. RESULTS: KO keratocyte conditioned media resulted in the greatest increase of CPAE cell proliferation (190.5+/-6.0%; p<0.01). WT keratocyte conditioned media showed higher CPAE proliferation (155.4+/-3.6%) than WT/MT1-MMP-transfected keratocytes (119.7+/-2.2%; p<0.001). Migration assays confirmed these findings. CONCLUSIONS: Keratocyte-derived MT1-MMP has anti-angiogenic effects in CPAE cells.