Tissue factor expression in human leukemic cells

Hair, Gregory A.; Padula, Stephen; Zeff, Richard A.; Schmeizl, Mark; Contrino, Josephine; Kreutzer, Donald L.; Moerloose, Phillipe de; Boyd, Andrew W.; Stanley, Irene J.; Burgess, Anthony W; Rickles, Frederick R.

doi:10.1016/0145-2126(95)00107-7

Cited by 54 publications

(42 citation statements)

References 37 publications

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“…The PCA in cultures of human cancer cells was previously shown to be associated with TF. 18) We confirmed that the human breast carcinoma MDA-MB-435 cells exhibited PCA and demonstrated that it depended on the presence of factors VII and X in the substrate plasma. As shown in Fig.…”

Section: Effects Of Dt-13 On Cell Proliferation In Hypoxiasupporting

confidence: 66%

The Saponin Monomer of Dwarf Lilyturf Tuber, DT-13, Reduces Human Breast Cancer Cell Adhesion and Migration during Hypoxia via Regulation of Tissue Factor

Sun

Lin

Zhao

et al. 2010

Biological & Pharmaceutical Bulletin

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In 2009, the most commonly diagnosed type of cancer among women in the United States was breast cancer, accounting for 27% (192370) of all new cancer cases.1) Despite improvements in detecting and treating the primary tumor, long-term survival is often compromised by the appearance of metastatic lesions in unrelated tissues such as the brain or bone.2) The metastatic dissemination of tumor cells requires the acquisition of biological properties including enhanced migratory behavior and the capacity to breach blood vessel walls and the dense collagenous matrix surrounding tumors.3,4) Currently, there is no effective therapy for this cancer in the advanced stages after metastasis, and new approaches are urgently needed to treat such a malignant disease.Hypoxia is an important factor that promotes cancer metastasis. 5,6) In contrast to established cell lines cultured under normal oxygen concentrations, tumors in the body grow under a specific internal environment characterized by much lower oxygen concentrations. Tissue factor (TF) is frequently over-expressed in human tumors and exhibits dual influences through its signaling and procoagulant activity. 7)In some cases, tumor cells were found to ectopically produce the main TF ligand, plasma protein factor VII, an observation that may suggest a cancer-specific 'autocrine' activation of the TF pathway.7) These new observations of TF suggest this unique molecule can be exploited in various ways to treat human cancer. As it is functionally involved in tumor initiation, growth and angiogenesis, TF could be a rational target for the development of agents to specifically kill tumor cells or block metastasis.8) Overall, several new findings related to TF create a fascinating prospect that this unique molecule could be explored in various ways to treat human cancer.Dwarf lilyturf tuber, a traditional Chinese medicinal (TCM) plant, is used widely in the clinics.9) The saponin monomer 13 of dwarf lilyturf tuber (DT-13), one of the saponin monomers of dwarf lilyturf tuber isolated from Ophiopogon japonicus (THUNB.) ker-Gaul, 9,10) has been found to exhibit anti-tumor effects.11) However, direct evidence for the mechanism of action of DT-13 on tumors during hypoxia is lacking. Interestingly, in our preliminary experiments, we found that DT-13 could inhibit hypoxia-induced adhesion of cancer cells. Thus, the purpose of this present study was to investigate the effects of DT-13 on human breast carcinoma metastasis in hypoxic conditions, and explore the possible mechanism of DT-13 against tumor metastases. MATERIALS AND METHODS Cell Lines and Cell CultureHuman breast carcinoma MDA-MB-435 cells were cultured as monolayers in Dulbecco's modified Eagle's medium media (DMEM, Gibco) supplemented with 10% fetal calf serum (FCS, Gibco), 100 U/ml penicillin and 100 mg/ml streptomycin. To create hypoxic conditions, 70-80% confluent cells were placed in an anaerobic chamber (HERAcell 150, Thermo) with 1% O 2 and 5% CO 2 at 37°C.Cytotoxicity Assays Inhibitory effects were determined using t...

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Section: Effects Of Dt-13 On Cell Proliferation In Hypoxiasupporting

confidence: 66%

The Saponin Monomer of Dwarf Lilyturf Tuber, DT-13, Reduces Human Breast Cancer Cell Adhesion and Migration during Hypoxia via Regulation of Tissue Factor

Sun

Lin

Zhao

et al. 2010

Biological & Pharmaceutical Bulletin

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“…It is currently assumed that neutrophils do not express TF in relevant amounts. 35 Hence, this finding could be explained by the binding of soluble TF to neutrophils by an as-yet unidentified receptor. This increase in TF ϩ neutrophils could also be reproduced by our in vitro experiments when whole blood was incubated with LPS concentrations that could also be reached after administration of the LPS bolus in our in vivo study (Figure 2).…”

Section: Discussionmentioning

confidence: 99%

Endotoxin-Induced Activation of the Coagulation Cascade in Humans

Pernerstorfer

Stohlawetz

Hollenstein

et al. 1999

ATVB

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Abstract-During Gram-negative septic shock, lipopolysaccharide (LPS, endotoxin) induces tissue factor (TF) expression.TF expression is mediated by nuclear factor B and amplified by activated platelets. TF forms a highly procoagulant complex with activated coagulation factor VII (FVIIa). Hence, we hypothesized that aspirin, which inhibits LPS-induced, nuclear factor B-dependent TF expression in vitro and platelet activation in vivo, may suppress LPS-induced coagulation in humans. Therefore, we studied the effects of aspirin on systemic coagulation activation in the established and controlled setting of the human LPS model. Thirty healthy volunteers were challenged with LPS (4 ng/kg IV) after intake of either placebo or aspirin (1000 mg). Acetaminophen (1000 mg) was given to a third group to control for potential effects of antipyresis. Neither aspirin nor acetaminophen inhibited LPS-induced coagulation. However, LPS increased the percentage of circulating TF ϩ monocytes by 2-fold. This increase was associated with a decrease in FVIIa levels, which reached a minimum of 50% 24 hours after LPS infusion. Furthermore, LPS-induced thrombin generation increased plasma levels of circulating polymerized, but not cross-linked, fibrin (ie, thrombus precursor protein), whereas levels of soluble fibrin were unaffected. In summary, a single 1000-mg dose of aspirin did not decrease LPS-induced coagulation. However, our study showed, for the first time, that LPS increases TF ϩ monocytes, substantially decreases FVIIa levels, and enhances plasma levels of thrombus precursor protein, which may be a useful marker of fibrin formation in humans. ). 1,2 DIC is defined by enhanced activity of coagulation factors, exhaustion of endogenous coagulation inhibitors, and activation and depletion of platelets by formation of thrombi in the vasculature. 3 Results of several studies suggest that initiation of coagulation in sepsis is driven primarily by the tissue factor (TF)-dependent pathway of coagulation. 4,5 Inhibition of the TF-dependent activation of coagulation using antibodies against TF or activated factor VII (FVIIa) completely prevents LPS-induced activation of coagulation in animals. 6 -8 Thus, inhibition of TF expression on monocytes during endotoxemia may present a promising therapeutic option for dampening the coagulation cascade. A recent in vitro study showed that acetylsalicylic acid (ASA) reduces LPS-induced TF expression on isolated monocytes. 9 Conversely, whole-blood experiments showed that ASA enhanced TF activity on monocytes. 10,11 Furthermore, TF expression on human monocytes is enhanced by the presence of granulocytes and activated platelets, suggesting an even more complex regulation of TF in vivo. [12][13][14][15][16] In addition, results of animal studies suggest that inhibition of thromboxane A 2 -mediated platelet activation may improve DIC induced by LPS. 3 Besides in vitro studies and experiments in animals, infusion of small doses of LPS into humans has emerged as a valuable tool to explore the pathogenesis ...

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“…TF is constitutively expressed by a variety of cell types including fibroblasts, glomerular epithelial cells, and tumor cells (Hair et al, 1996;Mackman, 1997). TF is also constantly present in the adventitia of blood vessels and is thought to provide a protective barrier that serves an important role in maintaining hemostasis of the vascular system.…”

Section: Role Of Cytokines In Promotion Of Thrombosismentioning

confidence: 99%

Role of Inflammatory Mediators in Thrombogenesis

Shebuski

Kilgore²

2002

J Pharmacol Exp Ther

228

169

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The role of inflammation in cardiovascular disease and especially in thrombogenesis has become increasingly recognized as an important component of the overall disease process. Plaque rupture promotes activation of the inflammatory response and increased expression of tissue factor (TF), which in turn acts as one of the major initiators of extrinsic coagulation. It is becoming apparent that the expression of TF on endothelial cells, underlying smooth muscle cells and monocytes is regulated, in part, by proinflammatory cytokines including tumor necrosis factor and IL-1. In addition to initiating coagulation, interaction of TF with the adhesion molecule, P-selectin, has been demonstrated to accelerate the rate and extent of fibrin formation and deposition. P-selectin is expressed on activated platelets and endothelium and serves as the receptor for the endogenous ligand, P-selectin glycoprotein-1 (PSGL-1), expressed on various leukocytic cell types. In addition to mediating transient interactions between endothelial cells and leukocytes, P-selectin has been reported to mediate adherence of platelets to monocytes and neutrophils via specific interaction with PSGL-1. P-selectin is rapidly cleaved off the surface of the platelet membrane and appears in the circulation as a soluble form, which has been reported to be elevated in patients with acute coronary syndromes including unstable angina and non-Q-wave myocardial infarction. This review will focus on the role of cytokines in mediating TF expression and also explore the significance of the relationship between P-selectin and tissue factor in thrombus generation. In addition, possible pharmacological mechanisms to interrupt this disease process will be discussed.

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Tissue factor expression in human leukemic cells

Cited by 54 publications

References 37 publications

The Saponin Monomer of Dwarf Lilyturf Tuber, DT-13, Reduces Human Breast Cancer Cell Adhesion and Migration during Hypoxia via Regulation of Tissue Factor

The Saponin Monomer of Dwarf Lilyturf Tuber, DT-13, Reduces Human Breast Cancer Cell Adhesion and Migration during Hypoxia via Regulation of Tissue Factor

Endotoxin-Induced Activation of the Coagulation Cascade in Humans

Role of Inflammatory Mediators in Thrombogenesis

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