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A Study of the Mechanism by Which Anticoagulation with Warfarin Inhibits Blood-borne Metastases¹

Department of Radiology, Stanford University School of Medicine, Stanford, California 94305

A study was made on the effect of warfarin-induced anticoagulation on the ability of KHT sarcoma cells to metastasize in syngeneic C3H mice. This anticoagulant effectively reduced the number of lung metastases resulting from a thigh-implanted tumor and also from an i.v. injection of a known number of cells. It was concluded, from several lines of investigation, that no part of the reduction in the number of metastases was due to cytotoxic or cytostatic properties of this anticoagulant.

The i.v. injection of iododeoxyuridine-¹²⁵I-labeled tumor cells showed that the lower number of metastases in the warfarin-treated mice was a result of an increased clearance of tumor cells from the lungs of anticoagulated mice between 6 and 24 hr after injection. The data are consistent with, but do not prove, the hypothesis that the reduction in blood-borne metastases by warfarin is due to the anticoagulation it produced, which prevented the formation of adequate thrombi around the endothelium-attached tumor cells, thereby keeping these cells vulnerable to the normal cell-mediated defense mechanisms.

¹ These studies were supported by American Cancer Society (California Division) Special Grant 548, by Stanford University General Research Support Grant 13, and by USPHS Research Grant CA-10372.

² Recipient of American Cancer Society (California Division) Dernham Senior Fellowship.

Received 10/30/72. Accepted 2/27/73.

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