Fibrinogen influx and accumulation of cross-linked fibrin in healing wounds and in tumor stroma.
Fibrinogen influx and accumulation of cross-linked fibrin in healing wounds and in tumor stroma.
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发表时间：
1988-03
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通讯作者：
L. Brown;L. Water;Harvey Vs;H. Dvorak
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作者：
L. Brown;L. Water;Harvey Vs;H. Dvorak
纤维蛋白原进入伤口和实体瘤，在那里它凝结成纤维蛋白，随后可能被胶原基质取代。如果，正如已经提出的，伤口愈合和肿瘤基质生成的发病机制是相似的，并依赖于纤维蛋白沉积，那么沉积在伤口和肿瘤中的纤维蛋白的类型和数量也可能是相似的。为了验证这一假设，作者将同源示踪剂纤维蛋白原（125 I-GPF）静脉注射到豚鼠体内，并测量其在皮肤伤口和同源癌中的流入和积聚。为了支持他们的假设，通过凝胶电泳将沉积在伤口和肿瘤中的尿素不溶性产物鉴定为交联纤维蛋白。总的和尿素不溶性125 I-GPF的积累在伤口和肿瘤中的定量相似。然而，125 I-GPF在肿瘤中的流入和初始凝血超过了伤口;考虑到等效的积累，这些数据表明，纤维蛋白周转在肿瘤中比在伤口中更快。纤维蛋白原流入和纤维蛋白积累下降到正常数天后受伤，但始终在肿瘤升高。因此，微血管通透性过高的程度和持续性以及纤维蛋白周转是区分肿瘤与愈合伤口的主要差异点。
Fibrinogen enters wounds and solid tumors, where it is clotted to fibrin that may subsequently be replaced by collagenous stroma. If, as has been suggested, the pathogenesis of wound healing and tumor stroma generation is similar and dependent on fibrin deposition, then the types and amounts of fibrin deposited in wounds and tumors might also be expected to be similar. To test this hypothesis, the authors injected homologous tracer fibrinogen (125I-GPF) intravenously into guinea pigs and measured its influx and accumulation in skin wounds and syngeneic carcinomas. In support of their hypothesis, the urea-insoluble product deposited in both wounds and tumors was identified as cross-linked fibrin by gel electrophoresis. Accumulation of both total and urea-insoluble 125I-GPF was quantitatively similar in wounds and tumors. However, influx and initial clotting of 125I-GPF in tumors exceeded that in wounds; given equivalent accumulation, these data suggest that fibrin turnover is more rapid in tumors than in wounds. Fibrinogen influx and fibrin accumulation declined toward normal a few days after wounding but remained consistently elevated in tumors. Thus, the magnitude and the persistence of microvascular hyperpermeability, as well as fibrin turnover, are major points of difference that distinguish tumors from healing wounds.