Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China; Department of General Surgery, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, China.
Department of Gastrointestinal Surgery, Affiliated Hospital of Nantong University, Medical school of Nantong University, Nantong, Jiangsu 226001, China; Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, China.
Acta Histochem. 2023 Aug;125(6):152071. doi: 10.1016/j.acthis.2023.152071. Epub 2023 Jun 16.
Serine protease 2 (PRSS2) is upregulated in gastric cancer tissues, correlates with poor prognosis and promotes migration and invasion of gastric cancer cells. However, the exact mechanism by which PRSS2 promotes metastasis in gastric cancer is unclear. We examined serum PRSS2 levels in healthy controls and gastric cancer patients by enzyme linked immunosorbent assay (ELISA) and analyzed the correlation between PRSS2 serum level with the clinicopathological characteristics of gastric cancer patients and matrix metalloproteinase-9 (MMP-9) expression. A lentiviral MMP-9 overexpression vector was constructed and used to transfect gastric cancer cells with stable silencing of PRSS2, and migration, invasion and epithelial-mesenchymal transition (EMT) of gastric cancer cells were examined. High serum PRSS2 levels were detected in gastric cancer patients and associated with lymphatic metastasis and TNM stage. Serum PRSS2 was positively correlated with serum MMP-9 level. PRSS2 silencing inhibited EMT, and knock-down of PRSS2 partially abrogated cell metastasis and EMT caused by overexpression of MMP-9. These results suggest that PRSS2 promotes the migration and invasion of gastric cancer cells through EMT induction by MMP-9. Our findings suggest that PRSS2 may be a potential early diagnostic marker and therapeutic target of gastric cancer.
丝氨酸蛋白酶 2（PRSS2）在胃癌组织中上调，与预后不良相关，并促进胃癌细胞的迁移和侵袭。然而，PRSS2 促进胃癌转移的确切机制尚不清楚。我们通过酶联免疫吸附测定（ELISA）检测了健康对照组和胃癌患者的血清 PRSS2 水平，并分析了 PRSS2 血清水平与胃癌患者的临床病理特征和基质金属蛋白酶-9（MMP-9）表达之间的相关性。构建了慢病毒 MMP-9 过表达载体，并用其转染稳定沉默 PRSS2 的胃癌细胞，并检测胃癌细胞的迁移、侵袭和上皮-间充质转化（EMT）。在胃癌患者中检测到高血清 PRSS2 水平，与淋巴转移和 TNM 分期相关。血清 PRSS2 与血清 MMP-9 水平呈正相关。PRSS2 沉默抑制 EMT，敲低 PRSS2 部分阻断了 MMP-9 过表达引起的细胞转移和 EMT。这些结果表明，PRSS2 通过 MMP-9 诱导 EMT 促进胃癌细胞的迁移和侵袭。我们的研究结果表明，PRSS2 可能是胃癌的一个潜在的早期诊断标志物和治疗靶点。
