Reduction of metastasis in a murine mammary tumour model by heparin and polyinosinic-polycytidylic acid.

A murine mammary tumour model has been used to test the efficacy of a combination of heparin and the interferon inducer, poly I:C on spontaneous metastasis from a s.c. primary tumour and on experimental metastasis following i.v. injection of tumour cells. This treatment has no effect on the growth of primary tumours, but lung metastases arising from these tumours were reduced. When tumour cells were injected i.v. the number of lung colonies was significantly reduced and survival time extended. Short-term treatment did not prevent the subsequent growth of extravasated, but dormant tumour cells, although mice treated for 8 or 12 weeks survived at least 6 months without any sign of lung colonies. Several mechanisms may contribute to the overall effect of this treatment; a reduction in the mitotic indices of lung colonies (observed in poly I:C treated mice) and also NK cells appeared to be important for the effectiveness of poly I:C since the reduction in experimental metastasis was abrogated by concomitant treatment with anti-asialo GM1 serum.