Circulating tumor cells and coagulation—Minireview

Bystricky, B.; Reuben, James M.; Mego, Michal

doi:10.1016/j.critrevonc.2017.04.003

Cited by 16 publications

(14 citation statements)

References 103 publications

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“…High levels of circulating neutrophils were also shown to correlate with an increased risk for cancer-related thrombosis [165,215]. This could be the result of the presence of NETs released by circulating neutrophils [216,217]. Neutrophilia seems therefore to reflect a systemic inflammatory response to cancer progression, leading to more pronounced NLR in advanced cancer [218].…”

Section: Cancer-related Circulating Neutrophils In Human Cancer Patientsmentioning

confidence: 99%

Cancer‐related circulating and tumor‐associated neutrophils – subtypes, sources and function

2018

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In recent years, the role of neutrophils in cancer biology has been a matter of increasing interest. Many patients with advanced cancer show high levels of neutrophilia, tumor neutrophils are connected to dismal prognosis, and the neutrophil-to-lymphocyte ratio has been introduced as a significant prognostic factor for survival in many types of cancer. Neutrophils constitute an important portion of the infiltrating immune cells in the tumor microenvironment, but controversy has long surrounded the function of these cells in the context of cancer. Multiple evidences have shown that neutrophils recruited to the tumor can acquire either protumor or antitumor function. These findings have led to the identification of multiple and heterogeneous neutrophil subsets in the tumor and circulation. In addition, tumor-associated neutrophils (TANs) were shown to demonstrate functional plasticity, driven by multiple factors present in the tumor microenvironment. In this review, we examine the current knowledge on cancer-related circulating neutrophils, their source and the function of the different subtypes, both mature and immature. We then discuss the pro vs antitumor nature of TANs in cancer, their functional plasticity and the mechanisms that regulate neutrophil recruitment and polarization. Although the vast majority of the knowledge on neutrophils in cancer comes from murine studies, recent work has been done on human cancer-related neutrophils. In the final paragraphs, we expand on the current knowledge regarding the role of neutrophils in human cancer and examine the question whether cancer-related neutrophils (circulating or intratumoral) could be a new possible target for cancer immunotherapy.

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Section: Cancer-related Circulating Neutrophils In Human Cancer Patientsmentioning

confidence: 99%

Cancer‐related circulating and tumor‐associated neutrophils – subtypes, sources and function

2018

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“…Hypercoagulability is actually a long known correlate of malignancy and venous thromboembolism has been associated with worse prognosis [10][11][12]. In particular, CTCs have recently been associated with increased risk of venous thrombosis in cancer patients [13][14][15][16]. Though cancer-associated thrombosis is clearly multifactorial, an aberrant thrombotic activity of tumor cells is considered a key factor.…”

Section: Introductionmentioning

confidence: 99%

“…If TF also triggers cellular signaling events that facilitate tumor progression [12,28,29], a determinant role of TF-associated coagulation mechanisms in supporting metastasis has been demonstrated [10,12,17,30,31]. Notwithstanding the implication of TF-bearing tumorderived microparticles in hypercoagulability, a local activation of coagulation is more particularly considered to contribute to the creation of a pericellular fibrin/platelet-rich cocoon protecting CTCs against shear stress, anoikis and immune attack and also providing a favorable niche for their early metastatic seeding [10,12,13,17,30,32].…”

Section: Introductionmentioning

confidence: 99%

Vimentin prevents a miR-dependent negative regulation of tissue factor mRNA during epithelial–mesenchymal transitions and facilitates early metastasis

et al. 2020

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Epithelial-mesenchymal transitions (EMTs) are high-profile in the field of circulating tumor cells (CTCs). EMT-shifted CTCs are considered to encompass pre-metastatic subpopulations though underlying molecular mechanisms remain elusive. Our previous work identified tissue factor (TF) as an EMT-induced gene providing tumor cells with coagulant properties and supporting metastatic colonization by CTCs. We here report that vimentin, the type III intermediate filament considered a canonical EMT marker, contributes to TF regulation and positively supports coagulant properties and early metastasis. Different evidence further pointed to a new post-transcriptional regulatory mechanism of TF mRNA by vimentin: (1) vimentin silencing accelerated TF mRNA decay after actinomycin D treatment, reflecting TF mRNA stabilization, (2) RNA immunoprecipitation revealed enriched levels of TF mRNA in vimentin immunoprecipitate, (3) TF 3′-UTR-luciferase reporter vector assays implicated the 3′-UTR of TF mRNA in vimentin-dependent TF regulation, and (4) using different TF 3′UTR-luciferase reporter vectors mutated for potential miR binding sites and specific Target Site Blockers identified a key miR binding site in vimentin-dependent TF mRNA regulation. All together, these data support a novel mechanism by which vimentin interferes with a miR-dependent negative regulation of TF mRNA, thereby promoting coagulant activity and early metastasis of vimentin-expressing CTCs.

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“…However, the risk of hypercoagulability is variable and is associated with cancer type. Hence, a clinical approach should be tailored according to the localization of the cancer, in as much as pancreatic, ovarian and brain cancers are at a higher risk of danger from thrombosis, intermediate risk is observed in colon and lung cancers, whereas breast and prostate cancers are at lower occurrence of thrombotic diathesis [ 2 , 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

Comprehensive analysis of haemostatic profile depending on clinicopathological determinants in breast cancer patients

Rhone¹,

Ruszkowska-Ciastek

Bielawski

et al. 2018

Bioscience Reports

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Thrombosis is one of the leading causes of mortality in cancer patients. The aim of the study was to evaluate the concentrations and activities of selected haemostatic parameters in the plasma of patients diagnosed with breast cancer (BrCa) and to make an attempt at finding associations with their levels and selected clinicopathological factors; clinical classification, histological grading, and molecular subtype of BrCa. The study involved 145 Caucasian ethnicity women. Eighty-five women aged 45–66 with primary BrCa without distant metastases (M0). Inclusion criteria were as follows: histopathological examination confirming the diagnosis of primary BrCa, without previous radiotherapy and chemotherapy. The control group consisted of 60, post-menopausal women, aged 45–68. Haemostatic profile expressed by concentrations and activities of tissue factor (TF) and its inhibitor (TFPI) as well as concentrations of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) were measured applying immunoassay techniques. A significantly higher concentration of PAI-1 was noted in patients with BrCa localized in the left breast. We observed significantly lower activity of TFPI and significantly higher concentration of PAI-1 in the group of patients with invasive ductal carcinoma as compared with invasive lobular carcinoma. A significantly higher concentration of t-PA in patients with pT2 BrCa in relation to pT1 cases was noted. Based on comprehensive analysis of haemostatic profile depending on clinicopathological features, we suggest that haemostatic parameters play crucial roles in invasion and metastases of malignant tumours.

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Circulating tumor cells and coagulation—Minireview

Cited by 16 publications

References 103 publications

Cancer‐related circulating and tumor‐associated neutrophils – subtypes, sources and function

Cancer‐related circulating and tumor‐associated neutrophils – subtypes, sources and function

Vimentin prevents a miR-dependent negative regulation of tissue factor mRNA during epithelial–mesenchymal transitions and facilitates early metastasis

Comprehensive analysis of haemostatic profile depending on clinicopathological determinants in breast cancer patients

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