Laiho M
Department of Virology, University of Helsinki, Finland.
Exp Cell Res. 1988 Jun;176(2):297-308. doi: 10.1016/0014-4827(88)90332-1.
We have previously described a factor(s) produced by 8387 fibrosarcoma cells, which can affect plasminogen activator (PA) activity of cultured cells. Since then, transforming growth factor-beta (TGF beta) has been established as a major growth factor/growth inhibitor that regulates both the expression and activity of PAs and their endothelial-type inhibitor (PAI-1). The present study was undertaken to characterize the 8387 fibrosarcoma cell-derived factor(s) and to investigate its relationships to TGF beta by analysis of modulation of PA activity and cell growth. The fibrosarcoma cell-derived proteins were partially purified from serum-free conditioned culture medium using Bio-Gel P-10 chromatography. Two separate fractions with apparent molecular weights of 16,000 and 12,000 contained activities that both decreased the secretion of PA activity by human lung fibroblasts and inhibited the soft agar growth of A549 lung adenocarcinoma cells. Both factors affected similarly the production of urokinase-type PA and PAI-1 in various cell lines and enhanced anchorage-independent growth of murine AKR-2B fibroblasts. The effects of these factors thus resembled those of TGF beta. The immunological relationships between the Mr 16,000 and Mr 12,000 factors and TGF beta were therefore studied using neutralizing anti-TGF beta antibodies. The TGF beta antibodies efficiently inhibited the effects of the Mr 16,000 factor but not those of the Mr 12,000 factor in cell culture assays. The results suggest that 8387 fibrosarcoma cells produce two major growth inhibitors, one of which is closely related to TGF beta.
我们之前曾描述过8387纤维肉瘤细胞产生的一种因子，它能够影响培养细胞的纤溶酶原激活物（PA）活性。从那时起，转化生长因子-β（TGF-β）已被确立为一种主要的生长因子/生长抑制剂，它可调节PA及其内皮型抑制剂（PAI-1）的表达和活性。本研究旨在对8387纤维肉瘤细胞衍生的因子进行特性鉴定，并通过分析PA活性和细胞生长的调节来研究其与TGF-β的关系。利用Bio-Gel P-10柱层析从无血清条件培养基中对纤维肉瘤细胞衍生的蛋白质进行部分纯化。两个表观分子量分别为16,000和12,000的独立组分具有以下活性：既能降低人肺成纤维细胞PA活性的分泌，又能抑制A549肺腺癌细胞在软琼脂中的生长。这两种因子对各种细胞系中尿激酶型PA和PAI-1的产生影响相似，并增强了小鼠AKR-2B成纤维细胞的非贴壁依赖性生长。因此，这些因子的作用类似于TGF-β。因此，使用中和抗TGF-β抗体研究了分子量为16,000和12,000的因子与TGF-β之间的免疫关系。在细胞培养试验中，TGF-β抗体有效抑制了分子量为16,000的因子的作用，但未抑制分子量为12,000的因子的作用。结果表明，8387纤维肉瘤细胞产生两种主要的生长抑制剂，其中一种与TGF-β密切相关。
