Abstract
MT1‐MMP (membrane type 1‐matrix metalloproteinase) plays important roles in cell growth and tumor invasion via mediating cleavage of MMP2/gelatinase A and a variety of substrates including type I collagen. BST‐2 (bone marrow stromal cell antigen 2) is a membrane tetherin whose expression dramatically reduces the release of a broad range of enveloped viruses including HIV from infected cells. In this study, we provided evidence that both transient and IFN‐α induced BST‐2 could decrease the activity of MMP2 via binding to cellular MT1‐MMP on its C‐terminus and inhibiting its proteolytic activity; and finally block cell growth and migration. Zymography gel and Western blot experiments demonstrated that BST‐2 decreased MMP2 activity, but no effect on the expression of MMP2 and MT1‐MMP genes. Confocal and immunoprecipitation data showed that BST‐2 co‐localized and interacted with MT1‐MMP. This interaction inhibited the proteolytic enzyme activity of MT1‐MMP, and blocked the activation of proMMP2. Experimental results of C‐terminus deletion mutant of MT1‐MMP showed that activity of MMP2 was no change and also no interaction existed between the mutant and BST‐2 after co‐transfection with the mutant and BST‐2. It meant that C‐terminus of MT1‐MMP played a key role in the interaction with BST‐2. In addition, cell growth in 3D type I collagen gel lattice and cell migration were all inhibited by BST‐2. Taken together, BST‐2, as a membrane protein and a tetherin of enveloped viruses, was a novel inhibitor of MT1‐MMP and could be considerable as an inhibitor of cancer cell growth and migration on clinic. J. Cell. Biochem. 113: 1013–1021, 2012. © 2011 Wiley Periodicals, Inc.