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American Journal of Pathology, Vol 130, 455-465, Copyright © 1988 by American Society for Investigative Pathology

REGULAR ARTICLES

Fibrinogen influx and accumulation of cross-linked fibrin in healing wounds and in tumor stroma

LF Brown, L Van de Water, VS Harvey and HF Dvorak
Department of Pathology, Beth Israel Hospital, Boston, Massachusetts 02215.

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.

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