Jankun J, Maher V M, McCormick J J
Department of Microbiology, Michigan State University, East Lansing 48824-1316.
Cancer Res. 1991 Feb 15;51(4):1221-6.
To determine whether a relationship exists among urokinase plasminogen activator (u-PA) activity, tissue plasminogen activator (t-PA) activity, and the malignant transformation of human fibroblasts, we measured receptor-bound and secreted u-PAs and t-PA activity in fibroblast cell strains of a unique cell lineage and compared the results with the values obtained in human fibrosarcoma-derived cell lines and control cell lines. The lineage consists of four nonmalignant, infinite life span cell strains, clonally derived from a finite life span, neonatal foreskin-derived cell line or one of its derivatives and 10 malignant cell strains clonally derived from that same derivative. Seven of the latter were malignantly transformed by K-, H-, or N-ras oncogene transfection, two were obtained following carcinogen treatment, and one arose spontaneously. All 10 malignant strains in this lineage exhibited significantly higher levels of activity of receptor-bound u-PA than was found in the cell strain from which they arose or the nonmalignant cell strains derived from it. The ras oncogene-transformed malignant strains also exhibited significantly higher levels of activity of receptor-bound t-PA than their cell strain of origin. The other three malignant strains showed undetectable levels, consistent with their attaining the malignant state by an alternate process. The five fully malignant fibrosarcoma-derived cell lines tested also showed high levels of receptor-bound u-PA and t-PA. The majority (greater than or equal to 80%) of the nonmalignant control cell lines did not do so. The 10 malignant cell strains in the lineage also exhibited higher levels of activity of secreted high molecular weight u-PA or t-PA than did their cell strain of origin and the nonmalignant cell strains derived from it, as did the malignant fibrosarcoma-derived cell lines. The data suggest that the malignant state of human fibroblasts is always associated with high levels of activity of receptor-bound u-PA, and in addition cells transformed to the malignant state are very likely to exhibit high levels of receptor-bound t-PA and secreted forms of plasminogen activators.
为了确定尿激酶型纤溶酶原激活剂（u-PA）活性、组织型纤溶酶原激活剂（t-PA）活性与人类成纤维细胞恶性转化之间是否存在关联，我们测量了一个独特细胞谱系的成纤维细胞株中与受体结合的和分泌的u-PA以及t-PA活性，并将结果与在人纤维肉瘤衍生细胞系和对照细胞系中获得的值进行比较。该谱系由四个非恶性、无限寿命的细胞株组成，它们是从一个有限寿命的新生儿包皮衍生细胞系或其衍生物之一克隆而来，还有10个恶性细胞株是从同一衍生物克隆而来。后者中的七个通过K-、H-或N-ras癌基因转染发生恶性转化，两个是在致癌物处理后获得的，一个是自发产生的。该谱系中的所有10个恶性株系与产生它们的细胞株或由此衍生的非恶性细胞株相比，均表现出与受体结合的u-PA活性水平显著更高。ras癌基因转化的恶性株系与受体结合的t-PA活性水平也显著高于其起源细胞株。其他三个恶性株系显示出无法检测到的水平，这与其通过另一种过程达到恶性状态一致。所测试的五个完全恶性的纤维肉瘤衍生细胞系也显示出高水平的与受体结合的u-PA和t-PA。大多数（大于或等于80%）非恶性对照细胞系则没有这种情况。该谱系中的10个恶性细胞株与产生它们的细胞株和由此衍生的非恶性细胞株相比，也表现出更高水平的分泌型高分子量u-PA或t-PA活性，纤维肉瘤衍生的恶性细胞系也是如此。数据表明，人类成纤维细胞的恶性状态总是与高水平的与受体结合的u-PA活性相关，此外，转化为恶性状态的细胞很可能表现出高水平的与受体结合的t-PA和纤溶酶原激活剂的分泌形式。
