Cancer and Translational Medicine Research Unit, Faculty of Medicine, University of Oulu, Oulu, Finland; Medical Research Center Oulu, Oulu University Hospital, University of Oulu, Oulu, Finland.
Cancer and Translational Medicine Research Unit, Faculty of Medicine, University of Oulu, Oulu, Finland; Medical Research Center Oulu, Oulu University Hospital, University of Oulu, Oulu, Finland; Biobank Borealis of Northern Finland, Oulu University Hospital, Finland.
Exp Cell Res. 2019 Mar 1;376(1):18-26. doi: 10.1016/j.yexcr.2019.01.018. Epub 2019 Jan 30.
Pro-tumorigenic activities of matrix metalloproteinase (MMP) 9 have been linked to many cancers, but recently the tumour-suppressing role of MMP9 has also been elucidated. The multifaceted evidence on this subject prompted us to examine the role of MMP9 in the behaviour of oral tongue squamous cell carcinoma (OTSCC) cells. We used gelatinase-specific inhibitor, CTT2, and short hairpin (sh) RNA gene silencing to study the effects of MMP9 on proliferation, motility and invasion of an aggressive OTSCC cell line, HSC-3. We found that the migration and invasion of HSC-3 cells were increased by CTT2 and shRNA silencing of MMP9. Proliferation, in turn, was decreased by MMP9 inhibition. Furthermore, arresten-overexpressing HSC-3 cells expressed increased levels of MMP9, but exhibited decreased motility compared with controls. Interestingly, these cells restored their migratory capabilities by CTT2 inhibition of MMP9. Hence, although higher MMP9 expression could give rise to an increased tumour growth in vivo due to increased proliferation, in some circumstances, it may participate in yet unidentified molecular mechanisms that reduce the cell movement in OTSCC.
基质金属蛋白酶（MMP）9 的促肿瘤生成活性与许多癌症有关，但最近也阐明了 MMP9 的肿瘤抑制作用。关于这个主题的多方面证据促使我们研究 MMP9 在口腔舌鳞状细胞癌（OTSCC）细胞行为中的作用。我们使用明胶酶特异性抑制剂 CTT2 和短发夹（sh）RNA 基因沉默来研究 MMP9 对侵袭性 OTSCC 细胞系 HSC-3 的增殖、迁移和侵袭的影响。我们发现 CTT2 和 MMP9 shRNA 沉默增加了 HSC-3 细胞的迁移和侵袭。相反，增殖则被 MMP9 抑制所减少。此外， arresten 过表达的 HSC-3 细胞表达了更高水平的 MMP9，但与对照相比，其迁移能力降低。有趣的是，这些细胞通过抑制 MMP9 恢复了它们的迁移能力。因此，尽管由于增殖增加，更高水平的 MMP9 表达可能导致体内肿瘤生长增加，但在某些情况下，它可能参与了尚未确定的分子机制，从而减少了 OTSCC 中的细胞运动。
