Affiliation:
1. From the Divisions of Hematology/Oncology and Developmental Biology, Children's Hospital Research Foundation and University of Cincinnati College of Medicine, Cincinnati, OH; and The Rockefeller University, New York, NY.
Abstract
Abstract
To test the hypothesis that platelet activation contributes to tumor dissemination, we studied metastasis in mice lacking Gαq, a G protein critical for platelet activation. Loss of platelet activation resulted in a profound diminution in both experimental and spontaneous metastases. Analyses of the distribution of radiolabeled tumor cells demonstrated that platelet function, like fibrinogen, significantly improved the survival of circulating tumor cells in the pulmonary vasculature. More detailed studies showed that the increase in metastatic success conferred by either platelets or fibrinogen was linked to natural killer cell function. Specifically, the pronounced reduction in tumor cell survival observed in fibrinogen- and Gαq-deficient mice relative to control animals was eliminated by the immunologic or genetic depletion of natural killer cells. These studies establish an important link between hemostatic factors and innate immunity and indicate that one mechanism by which the platelet-fibrin(ogen) axis contributes to metastatic potential is by impeding natural killer cell elimination of tumor cells.
Publisher
American Society of Hematology
Subject
Cell Biology,Hematology,Immunology,Biochemistry
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