Recruitment of monocytes/macrophages by tissue factor-mediated coagulation is essential for metastatic cell survival and premetastatic niche establishment in mice
Top Cited Papers
- 29 March 2012
- journal article
- research article
- Published by American Society of Hematology in Blood
- Vol. 119 (13), 3164-3175
- https://doi.org/10.1182/blood-2011-08-376426
Abstract
Tissue factor (TF) expression by tumor cells correlates with metastasis clinically and supports metastasis in experimental settings. However, the precise pathways coupling TF to malignancy remain incompletely defined. Here, we show that clot formation by TF indirectly enhances tumor cell survival after arrest in the lung, during experimental lung metastasis, by recruiting macrophages characterized by CD11b, CD68, F4/80, and CX3CR1 (but not CD11c) expression. Genetic or pharmacologic inhibition of coagulation, by either induction of TF pathway inhibitor ex-pression or by treatment with hirudin, respectively, abrogated macrophage recruitment and tumor cell survival. Furthermore, impairment of macrophage function, in either Mac1-deficient mice or in CD11b-diphtheria toxin receptor mice in which CD11b-positive cells were ablated, decreased tumor cell survival without altering clot formation, demonstrating that the recruitment of functional macrophages was essential for tumor cell survival. This effect was independent of NK cells. Moreover, a similar population of macrophages was also recruited to the lung during the formation of a premetastatic niche. Anticoagulation inhibited their accumulation and prevented the enhanced metastasis associated with the formation of the niche. Our study, for the first time, links TF induced coagulation to macrophage recruitment in the metastatic process.Keywords
This publication has 45 references indexed in Scilit:
- Cooperation of tissue factor cytoplasmic domain and PAR2 signaling in breast cancer developmentBlood, 2010
- Selectins promote tumor metastasisSeminars in Cancer Biology, 2010
- Procoagulant mechanisms in tumour cellsBest Practice & Research Clinical Haematology, 2009
- Tissue Factor Regulation by Epidermal Growth Factor Receptor and Epithelial-to-Mesenchymal Transitions: Effect on Tumor Initiation and AngiogenesisCancer Research, 2008
- Inhibition of tissue factor signaling suppresses tumor growthBlood, 2008
- Mechanisms linking tumor cell-associated procoagulant function to tumor metastasisThrombosis Research, 2007
- Tissue Factor and CancerPathophysiology of Haemostasis and Thrombosis, 2007
- Emerging Insights in Tissue Factor-Dependent Signaling EventsSeminars in Thrombosis and Hemostasis, 2006
- Cross-talk of Integrin α3β1 and Tissue Factor in Cell MigrationMolecular Biology of the Cell, 2004
- Regulation of angiogenesis by tissue factor cytoplasmic domain signalingNature Medicine, 2004