de Bruin P A, Griffioen G, Verspaget H W, Verheijen J H, Dooijewaard G, van den Ingh H F, Lamers C B
Department of Gastroenterology, University Hospital, Leiden, The Netherlands.
Cancer Res. 1988 Aug 15;48(16):4520-4.
Plasminogen activator (PA) activity, in particular urokinase (u-PA), has been shown to be markedly increased in adenocarcinomas of the colon. Adenomatous polyps were found to be intermediate in their PA activity to normal mucosa and adenocarcinomas. In the present study we evaluated the PA profile in relation to malignancy parameters of the adenomas. Forty-eight adenomatous polyps, obtained by endoscopic polypectomy, were scored according to size, histological type, and grade of dysplasia. In extracts, tissue-type PA (t-PA) and u-PA were determined using a spectrophotometric enzyme assay, antigen assays, and a bioimmunoassay for u-PA. Twenty-five paired samples of normal mucosa and adenocarcinoma were used as controls. Additionally, four hyperplastic polyps were studied by the same methods. The presence of complexes of PA with PA inhibitors was assessed by zymography. A 10-fold increase of u-PA antigen in carcinomas was found as compared to normal tissue. An increase was also noted in u-PA activity, although its extent was less, due to the fact that 74% of u-PA was in the inactive proenzyme form. Adenomatous polyps contained PA activities and antigens intermediate to those of normal mucosa and carcinomas, in accordance with the view that they are precursors in the development of colorectal cancer. Within the adenoma group, no relation was found between PA profile changes and histological type or polyp size. Surprisingly, in a group of four hyperplastic polyps, similar profiles of PA were found as in adenomas. When the u-PA/t-PA antigen ratio was taken as a parameter of developing malignancy, two discrete increases were seen during the adenoma-carcinoma sequence, the first at adenoma formation and the second accompanying the start of invasive growth in polyps with severe dysplasia. Zymography showed that only t-PA was present in complex with specific PA inhibitors, explaining how the decrease of t-PA activity in adenomas and carcinomas could be stronger than the parallel decrease of t-PA antigen, when these were compared with normal mucosa, which contained hardly any complexes.
纤溶酶原激活物（PA）活性，尤其是尿激酶（u-PA），在结肠癌腺癌中已显示出显著增加。腺瘤性息肉的PA活性介于正常黏膜和腺癌之间。在本研究中，我们评估了与腺瘤恶性参数相关的PA谱。通过内镜息肉切除术获得的48个腺瘤性息肉，根据大小、组织学类型和发育异常程度进行评分。在提取物中，使用分光光度酶测定法、抗原测定法和u-PA的生物免疫测定法测定组织型PA（t-PA）和u-PA。25对正常黏膜和腺癌样本用作对照。此外，用相同方法研究了4个增生性息肉。通过酶谱法评估PA与PA抑制剂复合物的存在。与正常组织相比，癌组织中u-PA抗原增加了10倍。u-PA活性也有所增加，尽管程度较小，因为74%的u-PA处于无活性的酶原形式。腺瘤性息肉的PA活性和抗原介于正常黏膜和癌组织之间，这与它们是结直肠癌发展的前体这一观点一致。在腺瘤组中，未发现PA谱变化与组织学类型或息肉大小之间存在关联。令人惊讶的是，在一组4个增生性息肉中，发现PA谱与腺瘤相似。当将u-PA/t-PA抗原比值作为恶性发展的参数时，在腺瘤-癌序列中观察到两个明显的增加，第一个在腺瘤形成时，第二个伴随重度发育异常息肉侵袭性生长的开始。酶谱法显示只有t-PA与特异性PA抑制剂形成复合物，这解释了与几乎不含任何复合物的正常黏膜相比，腺瘤和癌组织中t-PA活性的降低为何比t-PA抗原的平行降低更强。
