Enhanced Activity of Meprin-α, a Pro-Migratory and Pro-Angiogenic Protease, in Colorectal Cancer
Figure 1
Meprin promotes migration and angiogenesis in vitro.
(A) Parental MDCK wild-type cells (wt, open columns) and MDCK cells co-transfected with meprin-α and meprin-β (αβ, left panel, filled black columns) or transfected with either meprin-α (α) or meprin-β (β) alone (right panel, filled grey columns) were cultured on laminin 1-coated dishes and exposed to HGF (20 nM) to induce migration in the absence or presence of plasminogen as indicated. HGF-induced migration was tracked for 3–4 h using videomicroscopy. Shown is the average migration speed (+/− SEM) of meprin-transfected cells relative to identically treated wild-type cells. Results are the average from three to four independent experiments for each condition. In the presence of plasminogen (100 nM), HGF-induced migration of meprin-α/β co-transfected cells was significantly enhanced. This effect was reverted in the presence of the meprin inhibitor actinonin (100 nM). The migration of cells transfected with either meprin subunit alone was not different from wild-type cells. (B) Meprin-α promotes angiogenesis. Purified recombinant human active meprin-α was supplemented to the culture medium (0.7 µg/ml) in the rat aortic ring assay and outgrowth of vessels into the collagen gel was quantified using image analysis (see materials and methods). Nv: number of vessels, Nb: number of branchings, Lmax: maximum length of vessels. *p<0.05 compared to untreated organ culture. Results are from three independent experiments with triplicates for each condition.