@article{oai:kanazawa-u.repo.nii.ac.jp:00027556, author = {滝野, 隆久 and 宮森, 久志 and 佐藤, 博 and Kudo, Tomoya and Takino, Takahisa and Miyamori, Hisashi and Thompson, Erik W. and Sato, Hiroshi}, issue = {4}, journal = {Cancer Science}, month = {Apr}, note = {Although tissue inhibitor of metalloproteinase-2 (TIMP-2) is known to be not only an inhibitor of matrix metalloproteinases (MMP) but also a cofactor for membrane-type 1 MMP (MT1-MMP)-mediated MMP-2 activation, it is still unclear how TIMP-2 regulates MMP-2 activation and cleavage of substrates by MT1-MMP. In the present study we examined the levels of cell-surface MT1-MMP, MMP-2 activation and cleavage of MT1-MMP substrates in 293T cells transfected with the MT1-MMP and TIMP-2 genes. Co-expression of TIMP-2 at an appropriate level increased the level of cell-surface MT1-MMP, both the TIMP-2-bound and free forms, and generated processed MMP-2 with gelatin-degrading activity. In contrast, MT1-MMP substrates testican-1 and syndecan-1 were cleaved by the cells expressing MT1-MMP, which was inhibited by TIMP-2 even at levels that stimulate MMP-2 activation. These results suggest that TIMP-2 environment determines MT1-MMP substrate choice between direct cleavage of its own substrates and MMP-2 activation. © 2007 Japanese Cancer Association., 金沢大学がん研究所がん病態制御}, pages = {563--568}, title = {Substrate choice of membrane-type 1 matrix metalloproteinase is dictated by tissue inhibitor of metalloproteinase-2 levels}, volume = {98}, year = {2007} }