Platelets and fibrin(ogen) increase metastatic potential by impeding natural killer cell–mediated elimination of tumor cells

Joseph S. Palumbo; Kathryn E. Talmage; Jessica V. Massari; Christine M. La Jeunesse; Matthew J. Flick; Keith W. Kombrinck; Markéta Jirousková; Jay L. Degen

doi:10.1182/blood-2004-06-2272

journal article Jan 01, 2005

Platelets and fibrin(ogen) increase metastatic potential by impeding natural killer cell–mediated elimination of tumor cells

Joseph S. Palumbo Kathryn E. Talmage Jessica V. Massari Christine M. La Jeunesse Matthew J. Flick Keith W. Kombrinck Markéta Jirousková Jay L. Degen

Blood Vol. 105 No. 1 pp. 178-185 · American Society of Hematology

View at Publisher Save 10.1182/blood-2004-06-2272

Abstract

AbstractTo 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.

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References

Details

Published: Jan 01, 2005
Vol/Issue: 105(1)
Pages: 178-185

Authors

J

Joseph S. Palumbo