Brown L F, Chester J F, Malt R A, Dvorak H F
J Natl Cancer Inst. 1987 May;78(5):979-86.
Immunofluorescence studies have demonstrated the presence of fib (a group of fibrinogen- and fibrin-related proteins that react with antibodies raised against fibrinogen) in the stroma of several transplantable animal and autochthonous human tumors. Acceptance of these reports was tempered by the possibility of artifactual clotting and fibrinolysis associated with tumor removal or tumor transplantation and by the relatively poor histology inevitable when immunofluorescence is performed on frozen tissue sections. An immunoperoxidase study therefore was undertaken of the ductal pancreatic carcinomas induced in female LGV Syrian hamsters by N-nitroso-bis(2-oxopropyl)amine [(BOP) CAS: 60599-38-4]. Artifactual clotting and fibrinolysis associated with tumor removal were avoided by systemic anticoagulation and antifibrinolysis. Fibronectin and residual fib were prominent components of tumor stroma. Prominent fib deposits also were found in a new location: the basement membrane zones of atypical pancreatic ducts and invasive carcinomas. In contrast, fib deposits were never found in the basement membranes of blood vessels, nerves, or pancreatic acini of BOP-treated or normal animals, or in the ductal basement membranes in the normal pancreas. Ducts with marked atypicality and invasive pancreatic carcinomas frequently exhibited discontinuous basement membrane staining for fib, which often paralleled loss of staining for the integral basement membrane proteins--type IV collagen and laminin. Loss of acquired fib basement membrane staining with malignant disease progression may serve as a new marker for local tumor invasion.
免疫荧光研究已证实在几种可移植动物肿瘤和原发性人类肿瘤的基质中存在纤维蛋白原相关蛋白(一组与抗纤维蛋白原抗体发生反应的纤维蛋白原和纤维蛋白相关蛋白)。由于肿瘤切除或肿瘤移植可能导致人为凝血和纤维蛋白溶解,以及对冷冻组织切片进行免疫荧光检测时不可避免地存在相对较差的组织学情况,这些报告的可信度受到了影响。因此,我们对N-亚硝基双(2-氧代丙基)胺[(BOP),CAS:60599-38-4]诱导的雌性LGV叙利亚仓鼠胰腺导管癌进行了免疫过氧化物酶研究。通过全身抗凝和抗纤维蛋白溶解避免了与肿瘤切除相关的人为凝血和纤维蛋白溶解。纤连蛋白和残留的纤维蛋白原相关蛋白是肿瘤基质的主要成分。在一个新的位置也发现了显著的纤维蛋白原相关蛋白沉积:非典型胰腺导管和浸润性癌的基底膜区域。相比之下,在BOP处理的动物或正常动物的血管、神经或胰腺腺泡的基底膜中,以及正常胰腺的导管基底膜中从未发现纤维蛋白原相关蛋白沉积。具有明显非典型性的导管和浸润性胰腺癌经常表现出纤维蛋白原相关蛋白的基底膜染色不连续,这通常与完整基底膜蛋白——IV型胶原和层粘连蛋白的染色缺失平行。随着恶性疾病进展,获得性纤维蛋白原相关蛋白基底膜染色的丧失可能成为局部肿瘤侵袭的新标志物。