Extrapulmonary colony formation after intravenous injection of tumour cells into heparin-treated animals.

Recent data on extrapulmonary colony formation after heparin administration are inconclusive. A systematic study of this topic was undertaken with 4 experimental tumour systems and 2 distinct periods of reduced clotting capacity in rats and mice. I.v. injection of various numbers of tumour cells into i.p. heparinized animals leads to: (1) Significant reduction in the number of lung colonies. The effect after 9 h anti-coagulation is equal to or probably greater than after 2 h. (2) The reduction in the number of lung colonies caused by heparin is independent of the number of cells injected. (3) The number of extrapulmonary extrathoracic colonies is significantly increased by heparin in 3 of the 4 tumour systems. (4) The number of extrapulmonary intrathoracic colonies is probably unaffected. (5) The increase in extrapulmonary extrathoracic colony formation is not related to the degree of reduction in lung colonies. These data lead to the conclusion that the capacity of the lung capillaries to trap tumour cells can be decreased by heparin-induced alterations in fibrin formation. This results in a lodgement of tumour cells throughout the body which is far more pronounced than in animals with normal clotting capacity.