Effect of resection of localized pancreaticobiliary adenocarcinoma on angiogenic markers and tissue factor related pro-thrombotic and pro-angiogenic activity

Echrish, Hussein; Xiao, Yu; Madden, Leigh A.; Allgar, Victoria; Jp, Cooke; Wedgwood, K. R.; Dasgupta, Debanjali; Greenman, John; Maraveyas, Anthony

doi:10.1016/j.thromres.2014.05.022

Cited by 6 publications

(4 citation statements)

References 39 publications

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“…One study on 30 patients with pancreatic adenocarcinoma measured circulating TF-positive microvesicles both by flow-cytometry and by a functional procoagulant assay, and showed a slight reduction in the number of microvesicles with a significant reduction of microvesicle-TF procoagulant activity. 59 Interestingly, higher numbers of circulating TF-positive microvesicles or microvesicle-TF activity correlated with TF expression and microvessel density on tumour tissues. However, not all studies have shown a clear association between circulating microvesicle-TF activity and VTE occurrence in pancreatic cancer.…”

Section: Introductionmentioning

confidence: 93%

The relationship between pancreatic cancer and hypercoagulability: a comprehensive review on epidemiological and biological issues

et al. 2019

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It has long been recognised that pancreatic cancer induces a hypercoagulable state that may lead to clinically apparent thrombosis. Although the relationship between pancreatic cancer and hypercoagulability is well described, the underlying pathological mechanism(s) and the interplay between these pathways remain a matter of intensive study. This review summarises existing data on epidemiology and pathogenesis of thrombotic complications in pancreatic cancer with a particular emphasis on novel pathophysiological pathways. Pancreatic cancer is characterised by high tumoural expression of tissue factor, activation of leukocytes with the release of neutrophil extracellular traps, the dissemination of tumour-derived microvesicles that promote hypercoagulability and increased platelet activation. Furthermore, other coagulation pathways probably contribute to these processes, such as those that involve heparanase, podoplanin and hypofibrinolysis. In the era in which heparin and its derivatives—the currently recommended therapy for cancer-associated thrombosis—might be superseded by direct oral anticoagulants, novel data from mouse models of cancer-associated thrombosis suggest the possibility of future personalised therapeutic approaches. In this dynamic era for cancer-associated thrombosis, the discovery of novel prothrombotic and proinflammatory mechanisms will potentially uncover pharmacological targets to prevent and treat thrombosis without adversely affecting haemostasis.

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Section: Introductionmentioning

confidence: 93%

The relationship between pancreatic cancer and hypercoagulability: a comprehensive review on epidemiological and biological issues

et al. 2019

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“…Differences in association could be attributable to varying levels of TF encryption and the participation of TF in non‐coagulant activities, such as signaling of the TF–activated FVII (FVIIa) complex via protease‐activated receptor (PAR) 2 . In pancreatic cancer, increased levels of both TF‐MPs and MP TF activity have been significantly associated with VTE , and, furthermore, radical pancreatectomy in pancreatic cancer patients results in a significant decrease in the level of TF‐MPs , which is accompanied by a significant reduction in the level of procoagulant activity (PCA) . The exact contribution of TF‐MPs to the development of VTE may therefore be highly variable between tumor types, and the association with pancreatic cancer may reflect the high level of TF expression relative to other cancer types and/or the late stage of disease presentation .…”

Section: The Contribution Of Tf To Cancer‐associated Thrombosismentioning

confidence: 99%

Tissue factor‐bearing microparticles and inflammation: a potential mechanism for the development of venous thromboembolism in cancer

Date

Ettelaie

Maraveyas

2017

Journal of Thrombosis and Haemostasis

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Cancer is associated with an increased risk of venous thromboembolism (VTE); the exact mechanisms for the induction of VTE remain to be fully elucidated, but it is widely acknowledged that tissue factor (TF)-bearing microparticles (TF-MPs) may play a significant role. However, TF-MPs have yet to be accepted as a genuine biomarker for cancer-associated VTE, as the presence of elevated TF-MP levels is not always accompanied by thrombosis; interestingly, in certain cases, particularly in pancreatic cancer, VTE seems to be more likely in the context of acute inflammation. Although several potential mechanisms for the development of VTE in cancer have been postulated, this review explores the homeostatic disruption of TF-MPs, as the main reservoir of bloodborne TF, in the context of cancer and inflammation, and considers the abrogated responses of the activated endothelium and mononuclear phagocyte system in mediating this disruption.

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“…TF is also expressed on the surface of stromal cells and subsets of infiltrating inflammatory cells. Tumor-derived TF can be released from the tumor in the form of TF+ microvesicles that drive clot formation and thrombosis once entering the circulation as has been suggested in patient studies and mouse models [ 28 , 29 , 30 ].…”

Section: Thrombosis In Cancermentioning

confidence: 99%

Coagulation Signaling through PAR1 as a Therapeutic Target in Pancreatic Ductal Adenocarcinoma

Kothari

Flick

2021

IJMS

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Pancreatic ductal adenocarcinoma (PDAC) is a highly fatal disease with a 5-year survival rate of less than 10% following diagnosis. The aggressive and invasive properties of pancreatic cancer tumors coupled with poor diagnostic options contribute to the high mortality rate since most patients present with late-stage disease. Accordingly, PDAC is linked to the highest rate of cancer-associated venous thromboembolic disease of all solid tumor malignancies. However, in addition to promoting clot formation, recent studies suggest that the coagulation system in PDAC mediates a reciprocal relationship, whereby coagulation proteases and receptors promote PDAC tumor progression and dissemination. Here, upregulation of tissue factor (TF) by tumor cells can drive local generation of the central coagulation protease thrombin that promotes cell signaling activity through protease-activated receptors (PARs) expressed by both tumor cells and multiple stromal cell subsets. Moreover, the TF-thrombin-PAR1 signaling axis appears to be a major mechanism of cancer progression in general and PDAC in particular. Here, we summarize the current literature regarding the role of PAR1 in PDAC and review possibilities for pharmacologically targeting PAR1 as a PDAC therapeutic approach.

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Effect of resection of localized pancreaticobiliary adenocarcinoma on angiogenic markers and tissue factor related pro-thrombotic and pro-angiogenic activity

Cited by 6 publications

References 39 publications

The relationship between pancreatic cancer and hypercoagulability: a comprehensive review on epidemiological and biological issues

The relationship between pancreatic cancer and hypercoagulability: a comprehensive review on epidemiological and biological issues

Tissue factor‐bearing microparticles and inflammation: a potential mechanism for the development of venous thromboembolism in cancer

Coagulation Signaling through PAR1 as a Therapeutic Target in Pancreatic Ductal Adenocarcinoma

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