Platelet-tumor-cell interactions in mice. The role of platelets in the spread of malignant disease.

Abstract

AbstractThrombocytopenia reduces the number of metastases produced by a wide variety of murine tumors. Studies aimed at investigating interactions between tumors and platelets reveal that many tumors aggregated platelets in vitro and/or produced thrombocytopenia in vivo. In some instances, tumor‐cell‐induced thrombocytopenia in vivo was accompanied by accumulation of platelets in the lung. Thrombocytopenia was most active against metastases produced by tumors with the capacity to aggregate platelets in vitro and/or in vivo but it was also effective against metastases produced by tumors lacking such a capacity. Further studies, aimed at increasing platelet aggregation in vivo, as when fibroblasts were added to the tumor inoculum, or decreasing the platelet response to aggregating agents, as when aspirin was administered to mice, strongly support the role of platelet aggregation and the platelet release reaction in metastasis. As expected, fibroblasts enhanced while aspirin decreased tumor spread, the latter being equally effective against both artificially induced and spontaneously‐occurring metastases. Formation of platelet aggregates not only enhances but also seems to change the distribution of metastases. Tumors with platelet aggregating capacities usually give lung metastases while those devoid of such a capacity may show metastases of widespread distribution. Research with 125IUDR‐labelled B16 melanoma cells indicates that thrombocytopenia does not affect the initial vascular arrest of tumor cells but seems to influence their subsequent retention by the lung.