SLPI facilitates cell migration by regulating lamellipodia/ruffles and desmosomes, in which Galectin4 plays an important role

To elucidate the underlying mechanism of secretory leukocyte protease inhibitor (SLPI)-induced cell migration, we compared SLPI-deleted human gingival carcinoma Ca9-22 (ΔSLPI) cells and original (wild-type: wt) Ca9-22 cells using several microscopic imaging methods and gene expression analysis. Our results indicated reduced migration of ΔSLPI cells compared to wtCa9-22 cells. The lamellipodia/dorsal ruffles were smaller and moved slower in ΔSLPI cells compared to wtCa9-22 cells. Furthermore, well-developed intermediate filament bundles were observed at the desmosome junction of ΔSLPI cells. In addition, Galectin4 was strongly expressed in ΔSLPI cells, and its forced expression suppressed migration of wtCa9-22 cells. Taken together, SLPI facilitates cell migration by regulating lamellipodia/ruffles and desmosomes, in which Galectin4 plays an important role.

为阐明分泌性白细胞蛋白酶抑制剂（secretory leukocyte protease inhibitor, SLPI）诱导细胞迁移的潜在机制，本研究采用多种显微成像技术与基因表达分析方法，对比分析了SLPI缺失型人口腔牙龈癌Ca9-22细胞（ΔSLPI）与野生型（wild-type, wt）Ca9-22细胞。研究结果显示，相较于野生型Ca9-22细胞，ΔSLPI细胞的迁移能力显著减弱。ΔSLPI细胞的片状伪足/背部褶皱体积更小、运动速率更慢。此外，ΔSLPI细胞的桥粒连接处可见发育更为完备的中间丝束。进一步实验表明，半乳糖凝集素4（Galectin4）在ΔSLPI细胞中呈强表达状态，且其过表达可抑制野生型Ca9-22细胞的迁移能力。综上，SLPI可通过调控片状伪足/褶皱及桥粒通路促进细胞迁移，其中半乳糖凝集素4发挥了关键作用。