BACKGROUND The protein plasminogen activator inhibitor-1 (PAI-1), an inhibitor specific for urokinase plasminogen activator (uPA) and tissue plasminogen activator (tPA), has been shown to have a key role in cancer metastases. Currently, it is unknown as to whether the exocellular inhibition of PAI-1 can inhibit the migration of cancer cells. METHODS By fusing the mutated serine protease domain (SPD) of uPA and human serum albumin (HSA), PAItrap3, a protein that traps PAI-1, was synthesized and experiments were conducted to determine if exocellular PAItrap3 attenuates PAI-1-induced cancer cell migration in vitro. RESULTS PAItrap3 (0.8 μM) significantly inhibited the motility of MCF-7, MDA-MB-231, HeLa and 4T1 cancer cells, by 90%, 50%, 30% and 20%, respectively, without significantly altering their proliferation. The PAI-1-induced rearrangement of F-actin was significantly inhibited by PAItrap3, which produced a decrease in the number of cell protrusions by at least 20%. CONCLUSIONS In vitro, PAItrap3 inhibited PAI-1-induced cancer cell migration, mainly through inhibiting the rearrangement of F-actin. Overall, these results, provided they can be extrapolated to humans, suggest that the PAItrap3 protein could be used as an exocellular inhibitor to attenuate cancer metastases.

中文翻译：

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纤溶酶原激活物抑制剂（PAI）trap3是PAI-1的一种细胞外肽抑制剂，可减轻F-肌动蛋白的重排和癌细胞的迁移。

背景技术已经证明蛋白纤溶酶原激活物抑制剂-1（PAI-1）是一种针对尿激酶纤溶酶原激活物（uPA）和组织纤溶酶原激活物（tPA）的特异性抑制剂，在癌症转移中具有关键作用。目前，关于PAI-1的胞外抑制是否可以抑制癌细胞的迁移尚不清楚。方法将uPA的突变丝氨酸蛋白酶结构域（SPD）与人血清白蛋白（HSA）融合，合成捕获PAI-1的蛋白PAItrap3，并进行实验以确定胞外PAItrap3是否减弱PAI-1诱导的癌细胞。体外迁移。结果PAItrap3（0.8μM）显着抑制MCF-7，MDA-MB-231，HeLa和4T1癌细胞的活力，分别抑制90％，50％，30％和20％，而不会显着改变其增殖。PAItrap3可显着抑制PAI-1诱导的F-肌动蛋白重排，从而使细胞突起数量减少至少20％。结论在体外，PAItrap3主要通过抑制F-肌动蛋白的重排来抑制PAI-1诱导的癌细胞迁移。总体而言，这些结果（只要可以推断给人类）表明，PAItrap3蛋白可用作细胞外抑制剂来减轻癌症转移。