Kohga S, Harvey S R, Weaver R M, Markus G
Cancer Res. 1985 Apr;45(4):1787-96.
The immunoperoxidase technique, using antibodies against human urinary urokinase (Mr 55,000), was used for the localization of this enzyme in histological preparations of human colon tumors and normal colon tissue. The localization of tissue (vascular) activator was also investigated using antibodies against enzyme purified from human malignant melanoma. Both the "indirect method" and the peroxidase-antiperoxidase technique were found to be useful. Urokinase-reactive material was found in all tissues examined (33 primary cancers, 11 metastases, and 8 adenomas). In the normal colon, urokinase was found only in some of the goblet cells of the mucosal epithelium. In colon cancer, diffuse specific staining was observed in the cytoplasm, but the most intense staining was localized at the edge of the cancer cells bordering the lumen of the glands. In some cases, intense supranuclear staining could be observed in a location corresponding to the Golgi apparatus. In a few instances, urokinase could be seen associated with fibroblasts near the advancing front of an invading tumor. Adenoma, a benign tumor but often a precursor of cancer, also showed the presence of urokinase. Most significant were the observations showing that, in regions of the mucosal glands where normal epithelial cells were abruptly replaced by cancer cells, the appearance of cytoplasmic urokinase showed strict and exclusive association with the malignant cells, and the same was the case in transitions from normal epithelium to adenoma. In contrast to urokinase, tissue plasminogen activator was not associated with cancer cells, but was consistently present in the stroma which separates the cancer glands and was localized in the endothelium of the blood vessels. This visual evidence was supported by results of extraction of plasminogen activators from tumors, and from the separated mucosal and submucosal layers of the normal colon of the same patients, which showed that urokinase is most abundant in the tumor tissue and least abundant in the submucosa, while tissue activator is most prevalent in the well-vascularized mucosa and submucosa and scarce in the usually poorly vascularized adenocarcinomas.
采用抗人尿激酶（分子量55,000）抗体的免疫过氧化物酶技术，用于在人结肠肿瘤和正常结肠组织的组织学标本中定位这种酶。还使用抗从人恶性黑色素瘤中纯化的酶的抗体研究了组织（血管）激活剂的定位。发现“间接法”和过氧化物酶 - 抗过氧化物酶技术均有用。在所检查的所有组织（33例原发性癌、11例转移癌和8例腺瘤）中均发现了尿激酶反应性物质。在正常结肠中，仅在黏膜上皮的一些杯状细胞中发现尿激酶。在结肠癌中，在细胞质中观察到弥漫性特异性染色，但最强的染色位于癌细胞与腺腔相邻的边缘。在某些情况下，在对应于高尔基体的位置可观察到强烈的核上染色。在少数情况下，可看到尿激酶与侵袭性肿瘤前沿附近的成纤维细胞相关。腺瘤是一种良性肿瘤，但通常是癌症的前体，也显示存在尿激酶。最显著的观察结果表明，在黏膜腺区域，正常上皮细胞突然被癌细胞取代，细胞质尿激酶的出现与恶性细胞呈现严格且排他性的关联，从正常上皮向腺瘤转变时情况也是如此。与尿激酶相反，组织纤溶酶原激活剂与癌细胞无关，但始终存在于分隔癌腺的间质中，并定位于血管内皮。从肿瘤以及同一患者正常结肠分离的黏膜和黏膜下层中提取纤溶酶原激活剂的结果支持了这一视觉证据，结果表明尿激酶在肿瘤组织中含量最高，在黏膜下层中含量最低，而组织激活剂在血管丰富的黏膜和黏膜下层中最普遍，在通常血管较少的腺癌中稀少。
