Critical Analysis of Experimental Models for the Antimetastatic Effects of Anticoagulants

Abstract

It is well established that anticoagulant drugs have antimetastatic action in some experimental tumour models. Many investigations have shown a significant reduction in the number of secondary tumour deposits in anticoagulated animals (Hilgard and Thornes, 1976). Most of the evidence was derived from experiments in which tumour cells were injected intravenously and the animals subsequently monitored for tumour deposits in the lungs. Reviewing the available literature, it becomes apparent that the number of lung colonies can be reduced by a variety of different anticoagulant drugs such as heparin, ancrod, coumarin-derivatives and others. One might question whether this type of intrapulmonary tumour should be regarded as a true representation of spontaneous metastases. The intravenous injection of tumour cells into an experimental animal does not differ substantially from an intrapulmonary transplantation and probably has little in common with the pathophysiology of blood-borne metastases originating from a solid primary tumour. A more realistic approach to screening for the antimetastatic effects of drugs would be to measure their effects on spontaneous lung metastases derived from transplanted solid tumours. A review of the current literature on this topic reveals that only coumarin derivatives consistently bring about a reduction in spontaneous metastases; all other drugs give variable results (Table 1.).