Regulation of tissue factor in NT2 germ cell tumor cells by cisplatin chemotherapy

Jacobsen, Christine; Hauschild, Jessica; Steinemann, Gustav; Spath, Brigitte; Bokemeyer, Carsten; Ruf, Wolfram; Honecker, Friedemann

doi:10.1016/j.thromres.2015.07.002

Cited by 7 publications

(7 citation statements)

References 21 publications

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“…Cytotoxic agents activate cellular TF through induction of apoptosis/necrosis, which increases the availability of PS on the outer membrane leaflet [42,49]. THP1 cells were treated with daunorubicin (DNR) in the presence or absence of rutin or bacitracin for 24 h. As expected, DNR significantly enhanced TF-dependent PCA of THP1 cells (Figure 4B,C and Figure S7B) and increased PS membrane exposure (Figure 4D).…”

Section: Rutin Prevents Tf Activation On Thp1 Cells Through Downregulation Of Cryptic Tf Expressionsupporting

confidence: 58%

“…Following reverse transcription into cDNA with the Maxima First Strand cDNA Synthesis kit for RT-qPCR (ThermoFisher Scientific, Waltham, MA, USA), quantitative PCR was performed in triplicates with the SYBR ® Premix Ex Taq TM II Kit (TaKaRa Bio, Kusatsu, Japan) on a LightCycler ® 96 system (Roche, Basel, Switzerland). A total of 40 PCR cycles were carried out, each consisting of denaturation at 95 • C for 15 s, annealing at 58 • C for 5 s and extension at 72 • C for 26 s. Primer sequences for TF and GAPDH were as previously described [42]. Self-dimer formation of the primer pairs was initially excluded by gel electrophoresis (data not shown).…”

Section: Fxa Generation Assaymentioning

confidence: 99%

“…Inhibition of DNR-induced TF activation by bacitracin was confirmed using the monocytic leukemia cell line, U937 (Figure S8B). Cytotoxic agents activate cellular TF through induction of apoptosis/necrosis, which increases the availability of PS on the outer membrane leaflet [42,49]. THP1 cells were treated with daunorubicin (DNR) in the presence or absence of rutin or bacitracin for 24…”

Section: Rutin Prevents Tf Activation On Thp1 Cells Through Downregulation Of Cryptic Tf Expressionmentioning

confidence: 99%

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Bacitracin and Rutin Regulate Tissue Factor Production in Inflammatory Monocytes and Acute Myeloid Leukemia Blasts

Beckmann

Rolling

Voigtländer

et al. 2021

Cancers

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Aberrant expression of tissue factor (TF) by transformed myeloblasts and inflammatory monocytes drives coagulation activation in acute myeloid leukemia (AML). Although regulation of TF procoagulant activity (PCA) involves thiol-disulfide exchange reactions, the specific role of protein disulfide isomerase (PDI) and other thiol isomerases in AML-associated TF biology is unclear. THP1 cells and peripheral blood mononuclear cells (PBMCs) from healthy controls or AML patients were analyzed for thiol isomerase-dependent TF production under various experimental conditions. Total cellular and membrane TF antigen, TF PCA and TF mRNA were analyzed by ELISA, flow cytometry, clotting or Xa generation assay and qPCR, respectively. PBMCs and THP1 cells showed significant insulin reductase activity, which was inhibited by bacitracin or rutin. Co-incubation with these thiol isomerase inhibitors prevented LPS-induced TF production by CD14-positive monocytes and constitutive TF expression by THP1 cells and AML blasts. Downregulation of the TF antigen was mainly restricted to the cryptic pool of TF, efficiently preventing phosphatidylserine-dependent TF activation by daunorubicin, and at least partially regulated on the mRNA level in LPS-stimulated monocytes. Our study thus delineates a complex role of thiol isomerases in the regulation of myeloid TF PCA, with PDI being a promising therapeutic target in the management of AML-associated coagulopathies.

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Section: Rutin Prevents Tf Activation On Thp1 Cells Through Downregulation Of Cryptic Tf Expressionsupporting

confidence: 58%

Section: Fxa Generation Assaymentioning

confidence: 99%

Section: Rutin Prevents Tf Activation On Thp1 Cells Through Downregulation Of Cryptic Tf Expressionmentioning

confidence: 99%

See 1 more Smart Citation

Bacitracin and Rutin Regulate Tissue Factor Production in Inflammatory Monocytes and Acute Myeloid Leukemia Blasts

Beckmann

Rolling

Voigtländer

et al. 2021

Cancers

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“…The direct tumour effect on thrombin generation may be exaggerated after chemotherapy, providing one explanation for the ensuing heightened procoagulant state. For example, cisplatin, carboplatin, gemcitabine and paclitaxel all increased TF activity on lung cancer cells in vitro [155] and cisplatin treatment may cause an increase in TF in germ cell tumour cells [156]. It is suspected that one mechanism for increased risk of VTE during chemotherapy is apoptotic vesicles released upon death of the tumour cells, which appear to be more procoagulant than microvesicles and are sensitive to anti-TF inhibition (recently reviewed in [157]).…”

Section: Chemotherapy Effects On Thrombin Generationmentioning

confidence: 99%

Thrombin Generation and Cancer: Contributors and Consequences

Reddel

Tan

Chen

2019

Cancers

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The high occurrence of cancer-associated thrombosis is associated with elevated thrombin generation. Tumour cells increase the potential for thrombin generation both directly, through the expression and release of procoagulant factors, and indirectly, through signals that activate other cell types (including platelets, leukocytes and erythrocytes). Furthermore, cancer treatments can worsen these effects. Coagulation factors, including tissue factor, and inhibitors of coagulation are altered and extracellular vesicles (EVs), which can promote and support thrombin generation, are released by tumour and other cells. Some phosphatidylserine-expressing platelet subsets and platelet-derived EVs provide the surface required for the assembly of coagulation factors essential for thrombin generation in vivo. This review will explore the causes of increased thrombin production in cancer, and the availability and utility of tests and biomarkers. Increased thrombin production not only increases blood coagulation, but also promotes tumour growth and metastasis and as a consequence, thrombin and its contributors present opportunities for treatment of cancer-associated thrombosis and cancer itself.

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“…44 Cisplatininduced G2/M arrest also results in a procoagulant phenotype by accumulation of procoagulant TF on the cell membrane surface of germ cell tumors. 45 Tissue factor activity can also be regulated by oxidation or reduction in the Cys186-Cys209 disulfide bond at the Cterminal region of TF. Protein disulfide isomerase (PDI)-dependent oxidation and formation of the disulfide bond stimulates TF procoagulant activity by increasing the affinity of TF for FVIIa.…”

Section: Regulation Of Tissue Factor Transcription and Activitymentioning

confidence: 99%

Role of Tissue Factor in Tumor Progression and Cancer-Associated Thrombosis

Rondon

Kroone

Kapteijn

et al. 2019

Semin Thromb Hemost

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It has been long-established that cancer and thrombosis are linked, but the exact underlying pathological mechanism remains to be unraveled. As the initiator of the coagulation cascade, the transmembrane glycoprotein tissue factor (TF) has been intensely investigated for its role in cancer-associated thrombosis and cancer progression. TF expression is regulated by both specific oncogenes and environmental factors, and it is shown to regulate primary growth and metastasis formation in a variety of cancer models. In clinical studies, TF has been shown to be overexpressed in most cancer types and is strongly associated with disease progression. While TF clearly associates with cancer progression, a prominent role for TF in the development of cancer-associated thrombosis is less clear. The current concept is that cancer-associated thrombosis is associated with the secretion of tumor-derived TF-positive extracellular vesicles in certain tumor types. To date, many therapeutic strategies to target TF—both in preclinical and clinical phase—are being pursued, including targeting TF or the TF:FVIIa complex by itself or by exploiting TF as a docking molecule to deliver cytotoxic compounds to the tumor. In this review, the authors summarize the current understanding of the role of TF in both cancer progression and cancer-associated thrombosis, and discuss novel insights on TF as a therapeutic target as well as a biomarker for cancer progression and VTE.

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Regulation of tissue factor in NT2 germ cell tumor cells by cisplatin chemotherapy

Cited by 7 publications

References 21 publications

Bacitracin and Rutin Regulate Tissue Factor Production in Inflammatory Monocytes and Acute Myeloid Leukemia Blasts

Bacitracin and Rutin Regulate Tissue Factor Production in Inflammatory Monocytes and Acute Myeloid Leukemia Blasts

Thrombin Generation and Cancer: Contributors and Consequences

Role of Tissue Factor in Tumor Progression and Cancer-Associated Thrombosis

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