Brown L F, Asch B, Harvey V S, Buchinski B, Dvorak H F
Department of Pathology, Beth Israel Hospital, Boston, MA 02215.
Cancer Res. 1988 Apr 1;48(7):1920-5.
125I-radiolabeled guinea pig fibrinogen was used to measure the influx (20 min) and accumulation (18 h) of fibrinogen/fibrin in three transplantable carcinomas (Lewis lung, TA3/St mammary, and MOT ovarian) growing in the subcutaneous space of syngeneic mice. Fibrinogen influx and, to an even greater extent, fibrin accumulation were substantially increased in all three tumors, as compared with normal control tissues. A significantly larger fraction of tumor-associated than control tissue radioactivity was insoluble in 3 M urea, a property of cross-linked fibrin. Positive identification of cross-linked fibrin was made by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography of tumor extracts. Tumor fibrin deposits were localized by immunoperoxidase staining of tissue sections. Fibrin accumulation was also significantly increased in premalignant hyperplastic alveolar nodules that had been transplanted to cleared mammary fat pads, as compared with normal mammary tissue, and was further increased in primary mammary carcinomas that arose from hyperplastic alveolar nodules. These findings generalize to the mouse the principles that tumor vessels are hyperpermeable to plasma proteins and that fibrin accumulates in transplantable and primary tumors. Further, they demonstrate that tumor fibrin is cross-linked and therefore analogous to the fibrin deposited in thrombi, wounds, and cellular immunity.
使用¹²⁵I放射性标记的豚鼠纤维蛋白原，来测量同基因小鼠皮下生长的三种可移植癌（Lewis肺癌、TA3/St乳腺癌和MOT卵巢癌）中纤维蛋白原/纤维蛋白的流入量（20分钟）和积聚量（18小时）。与正常对照组织相比，所有三种肿瘤中的纤维蛋白原流入量，以及在更大程度上的纤维蛋白积聚量，均显著增加。与对照组织放射性相比，肿瘤相关放射性中显著更大比例的部分不溶于3M尿素，这是交联纤维蛋白的一种特性。通过肿瘤提取物的十二烷基硫酸钠-聚丙烯酰胺凝胶电泳和放射自显影，对交联纤维蛋白进行了阳性鉴定。通过组织切片的免疫过氧化物酶染色对肿瘤纤维蛋白沉积物进行定位。与正常乳腺组织相比，移植到清除乳腺脂肪垫中的癌前增生性肺泡结节中的纤维蛋白积聚也显著增加，并且在由增生性肺泡结节产生的原发性乳腺癌中进一步增加。这些发现将肿瘤血管对血浆蛋白具有高通透性以及纤维蛋白在可移植肿瘤和原发性肿瘤中积聚的原理推广到小鼠。此外，它们证明肿瘤纤维蛋白是交联的，因此类似于沉积在血栓、伤口和细胞免疫中的纤维蛋白。
