不同毒素或香烟烟雾的职业和环境暴露会引起非小细胞肺癌（NSCLC）；这是一种在转移后存活率非常低的破坏性疾病。高过氨酸蛋白酶（plasmin）的活性是NSCLC转移的一个特征。人们普遍认为，转移性细胞的plasmin活性比原发肿瘤细胞更高。然而，关于这种升高的机制，我们了解甚少。我们比较了源自原发肺肿瘤的A549细胞和从淋巴结中分离的转移性H1299肺细胞的plasmin活性和细胞迁移情况。令人惊讶的是，我们发现A549细胞的plasmin活性和迁移较高。H1299细胞中的plasmin原生物激活物抑制物-1（PAI-1）mRNA水平较高，细胞外调控激酶-1/2（ERK-1/2）的活性增加。ERK-1/2抑制剂降低了H1299细胞中PAI-1 mRNA水平，并增加了plasmin活性和细胞迁移。转化生长因子-β（TGF-β）降低了A549细胞的plasmin活性和迁移，但增加了H1299细胞中的两者。该细胞因子大大增加了A549细胞中的PAI-1，降低了尿激酶型plasmin原生物激活物（uPA）水平，但在H1299细胞中仅轻度诱导了uPA和PAI-1表达。因此，TGF-β增强了H1299细胞中的plasmin活性和细胞迁移。此外，TGF-β在H1299细胞中比在A549细胞中更强烈地激活了ERK-1/2。相应地，ERK-1/2抑制剂完全逆转了TGF-β对H1299细胞中uPA表达、plasmin活性和细胞迁移的影响。因此，我们首次提供了表明TGF-β促进了plasmin活性增加的数据，并建议阻断TGF-β促进的ERK-1/2活性可能是抑制NSCLC转移的直接方法。 ©2023. 作者。

Occupational and environmental exposure of various toxins or cigarette smoke causes non-small cell lung carcinoma (NSCLC); a devastating disease with a very low survival rate after metastasis. Increased activity of plasmin is a hallmark in NSCLC metastasis. It is accepted that metastatic cells exhibit higher plasmin activity than cells from primary tumors. Mechanisms behind this elevation, however, are barely understood. We compared plasmin activity and cell migration of A549 cells derived from a primary lung tumor with metastatic H1299 lung cells isolated from lymph nodes. Surprisingly, we found higher plasmin activity and migration for A549 cells. mRNA levels of the plasminogen activator inhibitor-1 (PAI-1) were higher in H1299 cells and activity of extracellular-regulated kinases-1/2 (ERK-1/2) was increased. An inhibitor of ERK-1/2 decreased PAI-1 mRNA levels and increased plasmin activity or cell migration in H1299 cells. Transforming growth factor-β (TGF-β) decreased plasmin activity and migration in A549 cells but enhanced both in H1299 cells. The cytokine massively increased PAI-1 and decreased urokinase plasminogen activator (uPA) levels in A549 cells but strongly induced uPA and only weakly PAI- 1 expression in H1299 cells. Consequently, TGF-β enhanced plasmin activity and cell migration in H1299. Additionally, TGF-β activated ERK-1/2 stronger in H1299 than in A549 cells. Accordingly, an ERK-1/2 inhibitor completely reversed the effects of TGF-β on uPA expression, plasmin activity and migration in H1299 cells. Hence, we provide first data indicating TGF-β-promoted increased plasmin activity and suggest that blocking TGF-β-promoted ERK-1/2 activity might be a straightforward approach to inhibit NSCLC metastasis.© 2023. The Author(s).