Crosstalk between cancer and haemostasis

Bokemeyer, Carsten

doi:10.5482/ha-1160

Cited by 57 publications

(11 citation statements)

References 99 publications

(105 reference statements)

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“…We now know that ADP induces P2Y 1 , and thromboxane A 2 stimulates TP, whereas thrombin acts through PAR1 or PAR4 [317]. In the case of thrombin activation, one of the primary initiators is tissue factor (TF), particularly in the case of tumor cells [318, 319, 317]. These platelet GPCRs, bind alpha regulatory subunits, G q alpha or G q/11 .…”

Section: Activating G Protein-coupled Receptorsmentioning

confidence: 99%

Platelets and cancer: a casual or causal relationship: revisited

Menter

Tucker

Kopetz

et al. 2014

Cancer Metastasis Rev

276

256

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Human platelets arise as subcellular fragments of megakaryocytes in bone marrow. The physiologic demand, presence of disease such as cancer, or drug effects can regulate the production circulating platelets. Platelet biology is essential to hemostasis, vascular integrity, angiogenesis, inflammation, innate immunity, wound healing, and cancer biology. The most critical biological platelet response is serving as “First Responders” during the wounding process. The exposure of extracellular matrix proteins and intracellular components occurs after wounding. Numerous platelet receptors recognize matrix proteins that trigger platelet activation, adhesion, aggregation, and stabilization. Once activated, platelets change shape and degranulate to release growth factors and bioactive lipids into the blood stream. This cyclic process recruits and aggregates platelets along with thrombogenesis. This process facilitates wound closure or can recognize circulating pathologic bodies. Cancer cell entry into the blood stream triggers platelet-mediated recognition and is amplified by cell surface receptors, cellular products, extracellular factors, and immune cells. In some cases, these interactions suppress immune recognition and elimination of cancer cells or promote arrest at the endothelium, or entrapment in the microvasculature, and survival. This supports survival and spread of cancer cells and the establishment of secondary lesions to serve as important targets for prevention and therapy.

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Section: Activating G Protein-coupled Receptorsmentioning

confidence: 99%

Platelets and cancer: a casual or causal relationship: revisited

Menter

Tucker

Kopetz

et al. 2014

Cancer Metastasis Rev

276

256

View full text Add to dashboard Cite

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“…Furthermore, strong TF expression in primary tumor samples suggested that this MP TF PCA was indeed cancer cell-derived. It is therefore tempting to speculate that, in addition to TF expressed by primary tumor cells, recruitment of TF-bearing MPs into the developing thrombus contributed to the formation of tumor cell microemboli by propagating further thrombin generation and fibrin deposition following separation of the TF-rich tumor cell surface from the flowing blood [1]. However, larger studies with more practical and better standardized assays for the measurement of MP-associated TF are needed to confirm these findings.…”

Section: Discussionmentioning

confidence: 99%

“…In mice, TF promotes hematogenous metastasis [1,3]. Specifically, coating of circulating tumor cells by fibrin(ogen)-platelet aggregates facilitates their firm adhesion to, and subsequent spreading on, the vascular endothelium and confers protection from natural killer cell-mediated cytotoxicity [4,13].…”

Section: Discussionmentioning

confidence: 99%

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Clinical Evidence that Coagulation Activation Drives Cancer Progression - a Report of 2 Cases

Voigtlaender

Holstein²,

Leuenroth³

et al. 2015

Oncol Res Treat

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Background: Tissue factor (TF), the principal initiator of the extrinsic coagulation pathway, is expressed by many tumors and can be released into the bloodstream on plasma microparticles (MPs). Experimental studies indicate that TF may facilitate hematogenous metastasis by promoting tumor cell-induced microvascular thrombosis, but clinical data supporting this hypothesis is sparse. Case Reports: Here, we report 2 unusual cases of rapidly progressive solid malignancies (gastric and urothelial carcinoma). In both patients, cancer cell dissemination with diffuse bone marrow involvement was either strongly suggested by leukoerythroblastic changes on peripheral blood smear or directly proven by positive findings on aspiration cytology. Furthermore, laboratory evidence of thrombotic microangiopathy (TMA) and disseminated intravascular coagulation was accompanied by new-onset severe pulmonary hypertension and a hemolytic uremic syndrome-like disorder in the gastric and the urothelial carcinoma patient, respectively. TF-specific procoagulant activity of isolated plasma MPs, as assessed by single-stage clotting assay, was dramatically increased in both patients compared to healthy controls (21- and 55-fold), and primary tumor samples stained strongly positive for TF by immunohistochemistry. Conclusion: TMA was likely caused by TF-triggered tumor cell embolization in both patients. Further clinical evidence is thus provided that TF directly links coagulation activation to cancer cell dissemination.

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“…Since the association and putative role of TF in CAT is extensively investigated and reviewed17, 18, 19, 20, 21 we will only briefly summarize the most important findings. TF is the activator of the extrinsic coagulation pathway, ultimately resulting in fibrin degradation and platelet activation.…”

Section: Tissue Factormentioning

confidence: 99%

Cancer‐associated thrombosis: The search for the holy grail continues

Ünlü

Versteeg

2018

Research and Practice in Thrombosis and Haemostasis

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Cancer patients have an increased risk of developing venous thromboembolism (VTE), a condition that is associated with increased morbidity and mortality. Although risk assessment tools have been developed, it is still very challenging to predict which cancer patients will suffer from VTE. The scope of this review is to summarize and discuss studies focusing on the link between genetic alterations and risk of cancer‐associated thrombosis (CAT). Thus far, classical risk factors that contribute to VTE have been tried as risk factors of CAT, with low success. In support, hypercoagulant plasma profiles in patients with CAT differ from those with only VTE, indicating other risk factors that contribute to VTE in cancer. As germline mutations do not significantly contribute to elevated risk of VTE, somatic mutations in tumors may significantly associate with and contribute to CAT. As it is very time‐consuming to investigate each and every mutation, an unbiased approach is warranted. In this light we discuss our own recent unbiased proof‐of‐principle study using RNA sequencing in isolated colorectal cancer cells. Our work has uncovered candidate genes that associate with VTE in colorectal cancer, and these gene profiles associated with VTE more significantly than classical parameters such as platelet counts, D‐dimer, and P‐selectin levels. Genes associated with VTE could be linked to pathways being involved in coagulation, inflammation and methionine degradation. We conclude that tumor cell‐specific gene expression profiles and/or mutational status has superior potential as predictors of VTE in cancer patients.

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Crosstalk between cancer and haemostasis

Cited by 57 publications

References 99 publications

Platelets and cancer: a casual or causal relationship: revisited

Platelets and cancer: a casual or causal relationship: revisited

Clinical Evidence that Coagulation Activation Drives Cancer Progression - a Report of 2 Cases

Cancer‐associated thrombosis: The search for the holy grail continues

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