The influence of fibrin formation on the transplantability of murine tumour cells: implications for the mechanism of the Révész effect

Br J Cancer. 1974 Apr;29(4):279-91. doi: 10.1038/bjc.1974.68.

Abstract

Experiments were undertaken to test a new hypothesis for the mechanism underlying the Révész effect. The hypothesis proposes that lethally irradiated (LI) tumour cells enhance the take probability of a small number of transplanted viable (V) tumour cells mixed with them by exerting a thromboplastic effect at the site of injection; local fibrin formation prevents emigration of V cells from the site or secures their survival there. The evidence presented to support this hypothesis is as follows: in the case of 3 isogeneically transplanted tumours, admixed particulate brain extract simulated the effect of LI cells in increasing the take probability of V cells; brain extract simulated the effect of LI cells in greatly delaying the disappearance of (125)IUdR-labelled viable carcinoma cells from the injection site; V cells acquired a raised take probability by their incorporation in fibrin clots; it was confirmed that admixed erythrocytes increased the take probability of V cells; using a newly devised microscopical test for detection of the thromboplastic activity of individual cells, it was found that cell death was almost always required for the display of such activity; lymphocytes and bone marrow cells, ineffective in enhancing the take of V cells, were almost totally devoid of thromboplastic activity. Possible explanations are given for failure of a fibrinogen depleting agent, ancrod (Arvin) to inhibit the Révész effect when administered to recipients. It is concluded that the evidence strongly supports the hypothesis presented whilst seriously weakening the long-standing theories that admixed LI cells act by provision of nutrients or by local quenching of postulated immune reactivity.

MeSH terms

  • Animals
  • Brain
  • Cell Line
  • Cell Survival / drug effects
  • Cell Survival / radiation effects
  • Fibrin / metabolism*
  • Leukemia, Experimental / metabolism
  • Mice
  • Mice, Inbred Strains
  • Neoplasm Metastasis
  • Neoplasm Transplantation*
  • Neoplasms / radiotherapy
  • Neoplasms, Experimental / metabolism*
  • Peptide Hydrolases / pharmacology
  • Radiation Effects*
  • Thromboplastin / metabolism
  • Tissue Extracts / pharmacology
  • Venoms / pharmacology

Substances

  • Tissue Extracts
  • Venoms
  • Fibrin
  • Thromboplastin
  • Peptide Hydrolases