Microparticle bearing tissue factor: A link between promyelocytic cells and hypercoagulable state

Gheldof, Damien; Mullier, François; Bailly, Nicolas; Devalet, Bérangère; Dogné, Jean‐Michel; Châtelain, Bernard; Chatelain, C

doi:10.1016/j.thromres.2013.11.008

Cited by 37 publications

(30 citation statements)

References 35 publications

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Section: Introductionmentioning

confidence: 99%

“…This phenomenon may be best explained by extracellular vesicles (EV), which are circular membrane compartments shed from cells, and when shed from cancer cells, mediate distal coagulation. 18 Compared to normal cells, cancer cells produce increased amounts of EV. 19,20 Cancer cellderived EV have generated particular interest in cancer related thrombosis due to their TF content, 18,21 and activation of procoagulant characteristics in endothelial cells.…”

Section: Introductionmentioning

confidence: 99%

“…18 Compared to normal cells, cancer cells produce increased amounts of EV. 19,20 Cancer cellderived EV have generated particular interest in cancer related thrombosis due to their TF content, 18,21 and activation of procoagulant characteristics in endothelial cells. 22 We previously showed that EV derived from leukemic mast cells could generate thrombin, and inhibit the process of fibrinolysis by increasing the expression and secretion of PAI-1.…”

Section: Introductionmentioning

confidence: 99%

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Thrombotic characteristics of extracellular vesicles derived from prostate cancer cells

et al. 2018

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The active oncogene EGFRvIII increases the concentration of TF and PAI-1 in EV. The procoagulant activity of EV is associated with the oncogenic and metastatic characteristics of their PC cells. Also, EV may contribute to the high procoagulant activity in the tumour microenvironment by the intercellular exchange of TF. Finally, through the generation of thrombin, EV can activate PAR-1, which evidently contributes to cancer progression, linking the coagulation system to tumor progression.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Thrombotic characteristics of extracellular vesicles derived from prostate cancer cells

et al. 2018

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“…The only acute promyelocytic leukemia included, expressed high levels of TF, a finding previously reported by others, and thought to contribute to the procoagulant state in these malignancies [25]. Although TF protein was absent by IHC in all patient-derived bone marrow biopsies with AML, we believe that it is likely that including a larger number of samples would likely detect a subset of positive cases, since tumor-cell-derived TF has been reported in leukemias of monocytic or promyelocytic origin.…”

Section: Discussionmentioning

confidence: 59%

Absence of tissue factor is characteristic of lymphoid malignancies of both T- and B-cell origin

Cesarman‐Maus

Braggio

Lome-Maldonado

et al. 2014

Thrombosis Research

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Summary Background Thrombosis is a marker of poor prognosis in individuals with solid tumors. The expression of tissue factor (TF) on the cell surface membrane of malignant cells is a pivotal molecular link between activation of coagulation, angiogenesis, metastasis, aggressive tumor behavior and poor survival. Interestingly, thrombosis is associated with shortened survival in solid, but not in lymphoid neoplasias. Objectives We sought to study whether the lack of impact of thrombosis on survival in lymphoid neoplasias could be due to a lack of tumor-derived TF expression. Methods We analyzed TF gene (F3) expression in lymphoid (N=114), myeloid (N=49) and solid tumor (N=856) cell lines using the publicly available dataset from the Broad-Novartis Cancer Cell Line Encyclopedia (http://www.broadinstitute.org/ccle/home), and in 90 patient-derived lymphoma samples. TF protein expression was studied by immunohistochemistry (IHC). Results In sharp contrast to wide F3 expression in solid tumors (74.2%), F3 was absent in all low and high grade T- and B-cell lymphomas, and in most myeloid tumors, except for select acute myeloid leukemias with monocytic component. IHC confirmed the absence of TF protein in all indolent and high-grade B-cell (0/90) and T-cell (0/20) lymphomas, and acute leukemias (0/11). Conclusions We show that TF in lymphomas does not derive from the malignant cells, since these do not express either F3 or TF protein. Therefore, it is unlikely that thrombosis in patients with lymphoid neoplasms is secondary to tumor-derived tissue factor.

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“…28 Tumor microparticles have PCA in vitro, but little is known about exosomes. 10,[29][30][31][32][33][34][35][36] The impact of EVs on fibrinolysis has also not been thoroughly investigated, but recent in vitro data suggest that tumor EVs might have a profibrinolytic activity. 37 We hypothesized that MSCs and clonal monocytes release EVs within the CMML TME, inducing a dysregulated coagulant state that could modify the homeostasis of HSCs and participate in the development of bone marrow dysfunction in CMML.…”

Section: Introductionmentioning

confidence: 99%

Tumor microenvironment and clonal monocytes from chronic myelomonocytic leukemia induce a procoagulant climate

et al. 2019

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Chronic myelomonocytic leukemia (CMML) is a myeloid hematological malignancy with overlapping features of myelodysplastic syndromes (MDSs) and myeloproliferative neoplasms (MPNs). The knowledge of the role of the tumor microenvironment (TME), particularly mesenchymal stromal cells (MSCs), in MDS pathogenesis is increasing. Generally, cancer is associated with a procoagulant state participating in tumor development. Monocytes release procoagulant, tissue factor (TF)–bearing microparticles. We hypothesized that MSCs and clonal monocytes release procoagulant extracellular vesicles (EVs) within the CMML TME, inducing a procoagulant state that could modify hematopoietic stem cell (HSC) homeostasis. We isolated and cultured MSCs and monocytes from CMML patients and MSCs from healthy donors (HDs). Their medium EVs and small EVs (sEVs) were collected after iterative ultracentrifugations and characterized by nanoparticle tracking analysis. Their impact on hemostasis was studied with a thrombin generation assay and fibrinography. CMML or HD HSCs were exposed to sEVs from either CMML or HD MSCs. CMML MSC sEVs increased HD HSC procoagulant activity, suggesting a transfer of TF from the CMML TME to HD HSCs. The presence of TF on sEVs was shown by electron microscopy and western blot. Moreover, CMML monocyte EVs conferred a procoagulant activity to HD MSCs, which was reversed by an anti-TF antibody, suggesting the presence of TF on the EVs. Our findings revealed a procoagulant “climate” within the CMML environment related to TF-bearing sEVs secreted by CMML MSCs and monocytes.

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Microparticle bearing tissue factor: A link between promyelocytic cells and hypercoagulable state

Cited by 37 publications

References 35 publications

Thrombotic characteristics of extracellular vesicles derived from prostate cancer cells

Thrombotic characteristics of extracellular vesicles derived from prostate cancer cells

Absence of tissue factor is characteristic of lymphoid malignancies of both T- and B-cell origin

Tumor microenvironment and clonal monocytes from chronic myelomonocytic leukemia induce a procoagulant climate

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