PLATELET CANCER CELL-INTERACTION IN METASTASIS FORMATION - POSSIBLE THERAPEUTIC APPROACH TO METASTASIS PROPHYLAXIS

  • 1 January 1977
    • journal article
    • research article
    • Vol. 8  (2) , 103-114
Abstract
The mechanism of the early stage of metastasis formation by sticky blood-born cancer cells is discussed. Abnormal platelet aggregation to circulating and lodged cancer cells, as well as alterations of blood coagulation and fibrinolysis play an important role. The reducing effect of several platelet aggregation inhibitors of cancer cell stickiness and tumor embolism mortality was investigated in rats after i.v. transplantation of 1 .times. 106 Walker-256 carcinosarcoma cells. The tested substances diminished platelet aggregation to circulating cancer cells, leading to a dose-dependent inhibition of cancer cell lodgment to the endothelium. Some of the substances prevented lethal pulmonary tumor cell embolism which was observed in 60% of the controls. These results are interpreted by assuming an inhibition of disseminated intravascular coagulation which occurred after i.v. transplantation of Walker-256 carcinosarcoma. On this basis a clinical long-term study for metastasis prophylaxis was started more than 4 yr ago with 1 of the tested substances, the dipyridamole derivative RA 233 [2,6-bis(diethanolamino-4-piperidino-pyrimido [4,4-d] pyrimidine], in 40 patients with sarcoma or malignant lymphoma of the head and neck region. The provisional results obtained in matched pairs are discussed.