Coagulation and metastasis: what does the experimental literature tell us?

Gil-Bernabé, Ana M.; Lucotti, Serena; Muschel, Ruth J.

doi:10.1111/bjh.12381

Cited by 100 publications

(83 citation statements)

References 95 publications

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“…Increasing literature today supports the involvement of coagulation events in cancer progression (13,14). The activation of coagulation has indeed long been correlated with malignancy and the beneficial impact of anticoagulants on cancer progression has been demonstrated in animal models (15)(16)(17) and evaluated in clinical studies (18).…”

Section: Introductionmentioning

confidence: 99%

“…Tissue factor (TF), a membrane-associated glycoprotein, has emerged as the central player in the relationship between the hemostatic system and cancer progression (13,14,(22)(23)(24)(25)(26). TF binds and activates coagulation factor FVII, which in turn triggers the downstream coagulation cascade leading to thrombin generation and clot formation.…”

Section: Introductionmentioning

confidence: 99%

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Tissue Factor Induced by Epithelial–Mesenchymal Transition Triggers a Procoagulant State That Drives Metastasis of Circulating Tumor Cells

et al. 2016

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Epithelial-mesenchymal transition (EMT) is prominent in circulating tumor cells (CTC), but how it influences metastatic spread in this setting is obscure. Insofar as blood provides a specific microenvironment for tumor cells, we explored a potential link between EMT and coagulation that may provide EMT-positive CTCs with enhanced colonizing properties. Here we report that EMT induces tissue factor (TF), a major cell-associated initiator of coagulation and related procoagulant properties in the blood. TF blockade by antibody or shRNA diminished the procoagulant activity of EMT-positive cells, confirming a functional role for TF in these processes. Silencing the EMT transcription factor ZEB1 inhibited both EMT-associated TF expression and coagulant activity, further strengthening the link between EMT and coagulation. Accordingly, EMT-positive cells exhibited a higher persistance/survival in the lungs of mice colonized after intravenous injection, a feature diminished by TF or ZEB1 silencing. In tumor cells with limited metastatic capability, enforcing expression of the EMT transcription factor Snail increased TF, coagulant properties, and early metastasis. Clinically, we identified a subpopulation of CTC expressing vimentin and TF in the blood of metastatic breast cancer patients consistent with our observations. Overall, our findings define a novel EMT-TF regulatory axis that triggers local activation of coagulation pathways to support metastatic colonization of EMT-positive CTCs.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Tissue Factor Induced by Epithelial–Mesenchymal Transition Triggers a Procoagulant State That Drives Metastasis of Circulating Tumor Cells

et al. 2016

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“…Most of the tumour cells introduced into the circulation are rapidly eliminated by shear stress or immune cells 4 . There is a plethora of studies indicating that the interaction of tumour cells with platelets within the bloodstream is essential during this early phase of metastasis [5][6][7] , and the ability of the circulating tumour cells to interact with platelets promote their survival within the circulation and therefore facilitate metastasis 4,5 . Platelets are involved in formation of a thrombus around tumour cells within the bloodstream, thus protecting tumour cells from shear stresses and natural killer (NK) cells lysis 8 .…”

mentioning

confidence: 99%

Platelets promote tumour metastasis via interaction between TLR4 and tumour cell-released high-mobility group box1 protein

et al. 2014

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Increasing evidence suggests that TLR4 expression by tumour cells promotes tumour progression, but it is unclear whether TLR4 is involved in metastasis. Here we show that TLR4 deficiency significantly diminishes experimental lung metastasis without affecting primary tumour growth. Bone marrow transplantation experiment and application of antiplatelet agents in mice demonstrate that TLR4 on platelets plays an important role in metastasis. TLR4 is critical for platelet-tumour cell interaction in vitro. Furthermore, high-mobility group box1 (HMGB1) neutralization attenuates platelet-tumour cell interaction in vitro and metastasis in vivo in a TLR4-dependent manner, indicating that tumour cell-released HMGB1 is the key factor that interacts with TLR4 on platelets and mediates platelet-tumour cell interaction, which promotes metastasis. These findings demonstrate a mechanism by which platelets promote tumour cell metastasis and suggest TLR4, and its endogenous ligand HMGB1 as targets for antimetastatic therapies.

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“…This is due to numerous risk factors specific for cancer patients: more frequent surgical interventions than in non-cancer patients, immobilisation due to pain, chemotherapy or infections, advanced age and medicines that increase the thrombosis risk (hormones, certain anti-cancer active substances). In addition, tumours themselves frequently activate coagulation, because activated coagulation factors and platelets support tumour growth and tumour cell dissemination (8,9).…”

Section: Zusammenfassungmentioning

confidence: 99%

Low molecular heparin for cancer-associated venous thromboembolism – still the “CATCH of the day“?

Matzdorff¹

2015

Phlebologie

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SummaryIn December 2014 the CATCH study was presented at the annual meeting of the American Society of Hematology. CATCH is a randomized controlled trial comparing the low molecular weight heparin tinzaparin with warfarin for 6 months extended treatment (=secondary prophylaxis) of cancer-associated venous thromboembolism (VTE). 6.9 % of patients in the tanzaparin arm experienced recurrent symptomatic and asymptomatic VTE compared with 10 % in the warfarin arm, this difference was statistically not significant. The difference became significant when only symptomatic VTEs were compared. There was no difference in the incidence of major bleeding events, but significantly fewer patients experienced clinically relevant non-major bleeding with tinzaparin than warfarin. The CATCH study is so far the largest study on extended treatment of cancer-associated VTE. It supports the guideline recommendation that low molecular weight heparins should be preferred to vitamin K antagonists for anticoagulation of cancer-associated VTE.

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Coagulation and metastasis: what does the experimental literature tell us?

Cited by 100 publications

References 95 publications

Tissue Factor Induced by Epithelial–Mesenchymal Transition Triggers a Procoagulant State That Drives Metastasis of Circulating Tumor Cells

Tissue Factor Induced by Epithelial–Mesenchymal Transition Triggers a Procoagulant State That Drives Metastasis of Circulating Tumor Cells

Platelets promote tumour metastasis via interaction between TLR4 and tumour cell-released high-mobility group box1 protein

Low molecular heparin for cancer-associated venous thromboembolism – still the “CATCH of the day“?

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