Evidence for effects of heparin on cell surfaces influencing experimental metastases

Abstract
The effect of heparin on tumour cells and on intravenously induced metastases was studied in a syngeneic tumour‐host system, MCG1‐SS in CBA mice. In vitro heparin induced significant changes in the volumes of cells, but did not affect their aggregability or vitality. In vivo heparin did not affect the subcutaneous transplantability of tumour cells. Metastasis formation from intravenously injected cells was differently affected when heparin was given as intravenous pretreatment to animals, than when the same amount was given in the cell suspensions. Thus, pretreatment of animals with heparin affected pulmonary metastases only to a small degree, but gave an increased number of tumour takes in extrapulmonary organs. These changes were ascribed to systemic effects of heparin, above all on blood coagulability.When given in the cell suspensions, heparin did not affect the number of extrapulmonary “takes”, but induced significant changes in pulmonary metastases. The average volume of such metastases became consistently smaller, while their number, if anything, rose. These effects were interpreted as being due to direct actions of heparin on the surfaces of tumour cells, probably related to its polyanion character. It was pointed out that in previous experiments with animals given large heparin doses, a direct cell effect might also prevail. Another polyanion, chondroitin sulphate, caused similar although less pronounced changes than heparin in vitro and in vivo. The polycation protamine had roughly opposite effects.