Kang T, Yi J, Yang W, Wang X, Jiang A, Pei D
Department of Pharmacology, University of Minnesota, Minneapolis, Minnesota 55455, USA.
FASEB J. 2000 Dec;14(15):2559-68. doi: 10.1096/fj.00-0269com.
MT3-MMP, a membrane-anchored matrix metalloproteinase, has been proposed to participate in the remodeling of extracellular matrix either by direct proteolysis or via activating other enzymes such as progelatinase A. To test this hypothesis, we analyzed the effect of exogenously transfected MT3-MMP in a tissue remodeling system: growth and tubulogenesis of Madin-Darby canine kidney (MDCK) cells in collagen gels. Although the parental cells require MMP activities for both growth and tubulogenesis, over-expression of wild-type MT3-MMP, but not its catalytically inactive mutant, leads to further enhancement of both processes, independent of its downstream substrate, progelatinase A. Mechanistically, MT3-MMP accomplishes such an effect by displaying on cell surfaces as active species, ready to activate progelatinase A or degrade ECM molecules. These data strongly suggest that MT3-MMP possesses the potential to directly enhance the growth and invasiveness of cells in vivo, two critical processes for development and carcinogenesis.
MT3-MMP是一种膜锚定基质金属蛋白酶，有人提出它可通过直接蛋白水解或激活其他酶（如前胶原酶A）参与细胞外基质的重塑。为验证这一假设，我们在一个组织重塑系统中分析了外源性转染MT3-MMP的作用：Madin-Darby犬肾（MDCK）细胞在胶原凝胶中的生长和管状形成。虽然亲代细胞的生长和管状形成都需要MMP活性，但野生型MT3-MMP的过表达，而非其催化失活突变体，会导致这两个过程进一步增强，且与下游底物前胶原酶A无关。从机制上讲，MT3-MMP通过在细胞表面以活性形式展示来实现这种作用，随时准备激活前胶原酶A或降解ECM分子。这些数据有力地表明，MT3-MMP具有直接增强体内细胞生长和侵袭性的潜力，这是发育和致癌过程中的两个关键过程。
