Koretz K, Möller P, Schwartz-Albiez R
Institut für Immunologie und Genetik, Deutsches Krebsforschungszentrum, Heidelberg, F.R.G.
Eur J Cancer. 1993;29A(8):1184-9. doi: 10.1016/s0959-8049(05)80312-0.
Plasminogen activators (PA) have been implicated with the degradation of extracellular matrix during the invasive growth of metastasising tumour cells. The significance of PA expression in tumour cells for the in vivo growth of malignant tumours is still a matter of debate. We, therefore, performed immunohistological studies on human colon tumours using monoclonal antibodies against urokinase- (u-PA) and tissue-type plasminogen activator (t-PA) as well as against plasminogen activator inhibitors 1 and 2 (PAI-1, PAI-2). Normal colorectal mucosa of seven samples was negative for all four constituents of the PA system. Tumour epithelium of 64 colorectal carcinomas and 10 liver metastases was consistently negative for both, PA and their inhibitors. However, two of four human colon carcinoma cell lines weakly expressed u-PA, PAI-1 and PAI-2. Intestinal dendritic or fibroblast-like cells within the tumour tissue strongly expressed u-PA and, at a lower level, also t-PA, PAI-1 and PAI-2. Vascular endothelial cells were weakly positive for all components of the PA system in colon carcinoma. Our findings indicate that colon carcinoma cells in their natural environment do not express constituents of the PA system. PA activity, previously found in colon carcinoma tissue, is most likely derived from interstitial cells.
纤溶酶原激活剂(PA)与转移性肿瘤细胞侵袭性生长过程中细胞外基质的降解有关。肿瘤细胞中PA表达对恶性肿瘤体内生长的意义仍存在争议。因此,我们使用抗尿激酶型纤溶酶原激活剂(u-PA)、组织型纤溶酶原激活剂(t-PA)以及抗纤溶酶原激活剂抑制剂1和2(PAI-1、PAI-2)的单克隆抗体,对人类结肠肿瘤进行了免疫组织学研究。7个样本的正常结直肠黏膜对PA系统的所有四种成分均呈阴性。64例结直肠癌和10例肝转移瘤的肿瘤上皮对PA及其抑制剂均持续呈阴性。然而,4个人类结肠癌细胞系中有2个弱表达u-PA、PAI-1和PAI-2。肿瘤组织内的肠道树突状或成纤维细胞样细胞强烈表达u-PA,t-PA、PAI-1和PAI-2表达水平较低。结肠癌中血管内皮细胞对PA系统的所有成分呈弱阳性。我们的研究结果表明,处于自然环境中的结肠癌细胞不表达PA系统的成分。先前在结肠癌组织中发现的PA活性很可能源自间质细胞。