Soeda S, Honda O, Shimeno H
Department of Biochemistry, Faculty of Pharmaceutical Sciences, Fukuoka University, Japan.
Cancer Lett. 1996 Nov 12;108(1):49-54. doi: 10.1016/s0304-3835(96)04392-3.
We constructed vascular endothelial cell monolayer on a fibronectin-coated filter in a Boyden chamber and assessed the ability of 3 LL cells to penetrate through the artificial blood vessel wall. The defense of endothelial cell monolayers against the tumor cell invasion was greatly potentiated by their pretreatment with 5 or 10 micrograms/ml of brefeldin A (BFA) for 1 h (52% or 28% of control invasion). Treatment of the endothelial cell monolayers with BFA resulted in an increase in the release of inhibitory material(s) against urokinase-type plasminogen activator (u-PA) activity of 3 LL cells. Parallel experiments with the cultured endothelial cells and BFA indicated that the fungal metabolite enhanced a rate of accumulation of plasminogen activator inhibitor-1 (PAI-1) antigen, but not of tissue-type plasminogen activator antigen in the medium. The BFA-induced enhancement of PAI-1 antigen release was accompanied with the increased accumulation of the extracellular (membrane/matrix-bound) and intracellular PAI-1 antigen (219% of control at 24 h). These results suggest that BFA can strengthen the defense of vascular endothelium against tumor-cell invasion by enhancing the release and accumulation of PAI-1, which plays a critical role in the regulation of the u-PA-plasmin-collagenase activation cascade.
我们在Boyden小室中用纤连蛋白包被的滤膜构建了血管内皮细胞单层，并评估了3LL细胞穿透人工血管壁的能力。用5或10微克/毫升布雷菲德菌素A（BFA）预处理内皮细胞单层1小时，可显著增强其对肿瘤细胞侵袭的防御能力（分别为对照侵袭的52%或28%）。用BFA处理内皮细胞单层导致针对3LL细胞尿激酶型纤溶酶原激活剂（u-PA）活性的抑制物质释放增加。用培养的内皮细胞和BFA进行的平行实验表明，这种真菌代谢产物提高了纤溶酶原激活剂抑制剂-1（PAI-1）抗原在培养基中的积累速率，但未提高组织型纤溶酶原激活剂抗原的积累速率。BFA诱导的PAI-1抗原释放增强伴随着细胞外（膜/基质结合）和细胞内PAI-1抗原积累的增加（24小时时为对照的219%）。这些结果表明，BFA可通过增强PAI-1的释放和积累来加强血管内皮对肿瘤细胞侵袭的防御，PAI-1在u-PA-纤溶酶-胶原酶激活级联反应的调节中起关键作用。
