Department of Molecular Pathology, Osaka University, Suita, Japan.
Biochem Biophys Res Commun. 2010 Mar 5;393(2):222-7. doi: 10.1016/j.bbrc.2010.01.105. Epub 2010 Feb 1.
The role of MT2-MMP in cancer progression remains to be elucidated in spite of many reports on MT1-MMP. Using a human fibrosarcoma cell, HT1080 and a human gastric cancer cell, TMK-1, endogenous expression of MT1-MMP or MT2-MMP was suppressed by siRNA induction to examine the influence of cancer progression in vitro and in vivo. In HT1080 cells, positive both in MT1-MMP and MT2-MMP, the migration as well as the invasion was impaired by MT1-MMP or MT2-MMP suppression. Also cell proliferation in three dimensional (3D) condition was inhibited by MT1-MMP or MT2-MMP suppression and tumor growth in the nude mice transplanted with tumor cells were reduced either MT1-MMP or MT2-MMP suppression with a prolongation of survival time in vivo. MT2-MMP suppression induces more inhibitory effects on 3D proliferation and in vivo tumor growth than MT1-MMP. On the other hand, TMK-1 cells, negative in MT1-MMP and MMP-2 but positive in MT2-MMP, all the migratory, invasive, and 3D proliferative activities in TMK-1 are decreased only by MT2-MMP suppression. These results indicate MT2-MMP might be involved in the cancer progression more than or equal to MT1-MMP independently of MMP-2 and MT1-MMP.
尽管有许多关于 MT1-MMP 的报道，但 MT2-MMP 在癌症进展中的作用仍有待阐明。本研究使用人纤维肉瘤细胞 HT1080 和人胃癌细胞 TMK-1，通过 siRNA 诱导抑制内源性 MT1-MMP 或 MT2-MMP 的表达，以体外和体内研究其对癌症进展的影响。在 HT1080 细胞中，MT1-MMP 和 MT2-MMP 均呈阳性，抑制 MT1-MMP 或 MT2-MMP 表达会损害细胞的迁移和侵袭能力。此外，抑制 MT1-MMP 或 MT2-MMP 表达会抑制细胞在三维（3D）条件下的增殖，并且裸鼠移植肿瘤细胞后肿瘤的生长也会减少，同时体内的生存时间也会延长。MT2-MMP 抑制对 3D 增殖和体内肿瘤生长的抑制作用比 MT1-MMP 更强。另一方面，TMK-1 细胞不表达 MT1-MMP 和 MMP-2，但表达 MT2-MMP，抑制 MT2-MMP 表达可降低 TMK-1 细胞的迁移、侵袭和 3D 增殖活性。这些结果表明，MT2-MMP 可能独立于 MMP-2 和 MT1-MMP 参与癌症进展的程度与 MT1-MMP 相当或更甚。
