Effects of tumor-expressed coagulation factors on cancer progression and venous thrombosis: is there a key factor?

Ünlü, Betül; Versteeg, Henri H.

doi:10.1016/s0049-3848(14)50013-8

Cited by 40 publications

(31 citation statements)

References 114 publications

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“…In addition, blockade of both host and tumor PAR-1 significantly decreased tumor cell metastatic potential. Similar results were obtained in melanoma models, thus confirming the contribution of thrombin-mediated PAR-1 activation to melanoma and breast metastases [160].…”

Section: Platelet Activation and Aggregationsupporting

confidence: 83%

Thrombin—unique coagulation system protein with multifaceted impacts on cancer and metastasis

Wojtukiewicz

Hempel

Sierko

et al. 2016

Cancer Metastasis Rev

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The association between blood coagulation and cancer development is well recognized. Thrombin, the pleiotropic enzyme best known for its contribution to fibrin formation and platelet aggregation during vascular hemostasis, may also trigger cellular events through protease-activated receptors, PAR-1 and PAR-4, leading to cancer progression. Our pioneering findings provided evidence that thrombin contributes to cancer metastasis by increasing adhesive potential of malignant cells. However, there is evidence that thrombin regulates every step of cancer dissemination: (1) cancer cell invasion, detachment from primary tumor, migration; (2) entering the blood vessel; (3) surviving in vasculature; (4) extravasation; (5) implantation in host organs. Recent studies have provided new molecular data about thrombin generation in cancer patients and the mechanisms by which thrombin contributes to transendothelial migration, platelet/tumor cell interactions, angiogenesis, and other processes. Though a great deal is known regarding the role of thrombin in cancer dissemination, there are new data for multiple thrombin-mediated events that justify devoting focus to this topic with a comprehensive approach.

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Section: Platelet Activation and Aggregationsupporting

confidence: 83%

Thrombin—unique coagulation system protein with multifaceted impacts on cancer and metastasis

Wojtukiewicz

Hempel

Sierko

et al. 2016

Cancer Metastasis Rev

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“…Both TF and PAR2 are over‐expressed in invasive cancer . Previous reports document the direct involvement of PAR2 in cancer cell proliferation, metastasis, and angiogenesis and in particular, PAR2 is highly associated with human breast cancer . PAR2 is also found to be essential for FVIIa and Xa‐induced signaling relating to migration and invasion of breast cancer cells .…”

Section: Introductionmentioning

confidence: 95%

Protease‐activated receptor 2 promotes actomyosin dependent transforming microvesicles generation from human breast cancer

Das

Prasad

Singh

et al. 2018

Molecular Carcinogenesis

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Apart from blood coagulation, coagulation proteases are involved inextricably in cancer progression/propagation via intra/inter-cellular signaling, mediated predominantly by protease-activated receptors (PARs). Microvesicles (MVs), a plasma membrane shredded component, has recently been identified as an important contributor to human breast cancer metastasis. However, the role of PAR2 in promoting MVs generation from breast cancer cells remains largely unexplored. The objective of this study is to investigate whether coagulation protease-mediated human breast cancer propagation commences via MVs and also to decipher the underlying signaling mechanism. Here, we elicited that coagulation factor-FVIIa and Trypsin activates PAR2, which governs MVs shedding from MDAMB231 cells by altering actomyosin dynamics. Treatment of cells with PAR2 activators facilitate MVs generation by activating three independent (MAPK, P38, and Rho) signaling cascades. MAPK, signals through activating MLCK followed by MLC phosphorylation to alter myosin organization whereas, P38 reorganizes actin dynamics by the sequential activation of MK2 and HSP27. RhoA-dependent ROCK-II activation again contributes to remodeling myosin II activity. Further, both our in vitro and in vivo analyses showed that these MVs potentiate invasive and migratory property to the recipient cells. Breast cancer patients blood show an elevation of TF-bearing, pro-metastatic MVs than normal. These findings give an insight into the detailed signaling mechanism involved in the production of MVs with transforming ability from PAR2-activated human breast cancer cells. Understanding these mechanistic details will certainly help to identify crucial targets for therapeutic interventions in MVs-associated human breast cancer metastasis.

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“…Associations between elevated MPs levels and an increased risk of VTE have been found in patients with underlying diseases such as high-grade glioma [90] or in patients undergoing in vitro fertilization [91] to treat infertility. However, confusion and contradictions are still present in clinical studies [92, 93]. Further research should focus on the following problems:

The limitations of current assays in measuring MPs may be divided into sizing, probing, and counting [94].

…”

Section: Microparticles: a Potential Biomarker For Ptementioning

confidence: 99%

Recent Progress in Research on the Pathogenesis of Pulmonary Thromboembolism: An Old Story with New Perspectives

Yan

Wang

et al. 2017

BioMed Research International

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Pulmonary thromboembolism (PTE) is part of a larger clinicopathological entity, venous thromboembolism. It is also a complex, multifactorial disorder divided into four major disease processes including venous thrombosis, thrombus in transit, acute pulmonary embolism, and pulmonary circulation reconstruction. Even when treated, some patients develop chronic thromboembolic pulmonary hypertension. PTE is also a common fatal type of pulmonary vascular disease worldwide, but earlier studies primarily focused on the pathological changes in the blood component of the disease. With contemporary advances in molecular and cellular biology, people are becoming increasingly aware of coagulation pathways, the function of vascular smooth muscle cells, microparticles, and the inflammatory pathways that play key roles in PTE. Combined hypoxia and immune research has revealed that PTE should be regarded as a class of complex diseases caused by multiple factors involving the vascular microenvironment and vascular cell dysfunction.

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Effects of tumor-expressed coagulation factors on cancer progression and venous thrombosis: is there a key factor?

Cited by 40 publications

References 114 publications

Thrombin—unique coagulation system protein with multifaceted impacts on cancer and metastasis

Thrombin—unique coagulation system protein with multifaceted impacts on cancer and metastasis

Protease‐activated receptor 2 promotes actomyosin dependent transforming microvesicles generation from human breast cancer

Recent Progress in Research on the Pathogenesis of Pulmonary Thromboembolism: An Old Story with New Perspectives

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