Buø L, Bjørnland K, Karlsrud T S, Kvale D, Kjønniksen I, Fodstad O, Brandtzaeg P, Johansen H T, Aasen A O
Institute for Surgical Research, Rikshospitalet Oslo, Norway.
Anticancer Res. 1994 Nov-Dec;14(6B):2445-51.
Plasminogen activators (PAs) and their inhibitors (PAIs) can be produced by tumor cells and surrounding inflammatory cells and fibroblasts. The present study evaluate both the expression and release of PAs (uPA and tPA) and PAIs (PAI-1 and PAI-2) from cultured cells, and also the expression of uPA receptor (uPAR). Immunocytochemistry showed that PAs, PAIs and uPAR were present to different extents on the surface of colon carcinoma cells (Caco-2, HT-29), malignant melanoma cells (LOX) and normal fibroblasts. uPA immunoreactivity was intermediate in Caco-2, HT-29 and LOX and weak in the fibroblasts. tPA immunoreactivity was intermediate in Caco-2 and LOX and weak in HT-29 and fibroblasts. PAI-1 and PAI-2 immunoreactivities were absent in HT-29, weak in Caco-2 and strong in fibroblasts. In LOX the immunoreactivity was intermediate for PAI-1 and strong for PAI-2. uPAR immunoreactivity was weak in Caco-2, HT-29 and LOX and negative in fibroblasts. ELISAs on conditioned medium detected that the colon carcinoma cells Caco-2 and HT-29 did not release any PAs or PAIs. LOX released tPA (median 9 ng/million cells at 72 hours), PAI-1 (1050 ng/million cells) and PAI-2 (245 ng/million cells), and fibroblasts released uPA (1 ng/million cells) and PAI-1 (910 ng/million cells). These results show that both tumor cells and fibroblasts express tissue destructive enzymes, PAs and PAIs, whereas only the tumor cells express the uPAR required for focalization and regulation of PA activity at the cell surface. The melanoma cells LOX and fibroblasts also released PAs and PAIs, in contrast to the colon carcinoma cells Caco-2 and HT-29.
纤溶酶原激活剂（PAs）及其抑制剂（PAIs）可由肿瘤细胞、周围炎性细胞和成纤维细胞产生。本研究评估了培养细胞中PAs（尿激酶型纤溶酶原激活剂[uPA]和组织型纤溶酶原激活剂[tPA]）和PAIs（PAI-1和PAI-2）的表达与释放情况，同时也评估了uPA受体（uPAR）的表达。免疫细胞化学显示，PAs、PAIs和uPAR在结肠癌细胞（Caco-2、HT-29）、恶性黑色素瘤细胞（LOX）和正常成纤维细胞表面有不同程度的表达。uPA免疫反应性在Caco-2、HT-29和LOX细胞中为中等强度，在成纤维细胞中较弱。tPA免疫反应性在Caco-2和LOX细胞中为中等强度，在HT-29细胞和成纤维细胞中较弱。PAI-1和PAI-2免疫反应性在HT-29细胞中未检测到，在Caco-2细胞中较弱，在成纤维细胞中较强。在LOX细胞中，PAI-1免疫反应性为中等强度，PAI-2免疫反应性较强。uPAR免疫反应性在Caco-2、HT-29和LOX细胞中较弱，在成纤维细胞中呈阴性。对条件培养基进行酶联免疫吸附测定（ELISAs）发现，结肠癌细胞Caco-2和HT-29不释放任何PAs或PAIs。LOX细胞释放tPA（72小时时中位数为9纳克/百万细胞）、PAI-1（1050纳克/百万细胞）和PAI-2（245纳克/百万细胞），成纤维细胞释放uPA（1纳克/百万细胞）和PAI-1（910纳克/百万细胞）。这些结果表明，肿瘤细胞和成纤维细胞均表达组织破坏性酶PAs和PAIs，而只有肿瘤细胞表达细胞表面PA活性聚焦和调节所需的uPAR。与结肠癌细胞Caco-2和HT-29不同，黑色素瘤细胞LOX和成纤维细胞也释放PAs和PAIs。
