Tissue Factor–Factor VII Complex as a Key Regulator of Ovarian Cancer Phenotypes

Tissue factor (TF) is an integral membrane protein widely expressed in normal human cells. Blood coagulation factor VII (fVII) is a key enzyme in the extrinsic coagulation cascade that is predominantly secreted by hepatocytes and released into the bloodstream. The TF–fVII complex is aberrantly expressed on the surface of cancer cells, including ovarian cancer cells. This procoagulant complex can initiate intracellular signaling mechanisms, resulting in malignant phenotypes. Cancer tissues are chronically exposed to hypoxia. TF and fVII can be induced in response to hypoxia in ovarian cancer cells at the gene expression level, leading to the autonomous production of the TF–fVII complex. Here, we discuss the roles of the TF–fVII complex in the induction of malignant phenotypes in ovarian cancer cells. The hypoxic nature of ovarian cancer tissues and the roles of TF expression in endometriosis are discussed. Arguments will be extended to potential strategies to treat ovarian cancers based on our current knowledge of TF–fVII function.

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Self-production of tissue factor-coagulation factor VII complex by ovarian cancer cells

British Journal of Cancer ◽

10.1038/sj.bjc.6605406 ◽

2009 ◽

Vol 101 (12) ◽

pp. 2023-2029 ◽

Cited By ~ 41

Author(s):

N Yokota ◽

S Koizume ◽

E Miyagi ◽

F Hirahara ◽

Y Nakamura ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Tissue Factor ◽

Coagulation Factor ◽

Factor Vii ◽

Ovarian Cancer Cells ◽

Coagulation Factor Vii ◽

Self Production

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Circulating Tissue Factor Procoagulant Activity and Thrombin Generation in Patients with Type 2 Diabetes: Effects of Insulin and Glucose

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2007-0933 ◽

2007 ◽

Vol 92 (11) ◽

pp. 4352-4358 ◽

Cited By ~ 83

Author(s):

Guenther Boden ◽

Vijender R. Vaidyula ◽

Carol Homko ◽

Peter Cheung ◽

A. Koneti Rao

Keyword(s):

Type 2 Diabetes ◽

Tissue Factor ◽

Blood Coagulation ◽

Coagulation Factor ◽

Procoagulant Activity ◽

Factor Vii ◽

Coagulation Factor Vii ◽

Glucose Levels ◽

Study Protocols

Abstract Context: Type 2 diabetes mellitus (T2DM) is a hypercoagulable state. Tissue factor (TF) is the principal initiator of blood coagulation. Objective: Our objective was to examine the effects of hyperglycemia and hyperinsulinemia on the TF pathway of blood coagulation in T2DM. Design: Three study protocols were used: 1) acute correction of hyperglycemia (with iv insulin) followed by 24 h of euglycemia, 2) 24 h of selective hyperinsulinemia, and 3) 24 h of combined hyperinsulinemia and hyperglycemia. Setting: The study took place at a clinical research center. Study Participants: Participants included 18 T2DM patients and 22 nondiabetic controls. Results: Basal TF-procoagulant activity (TF-PCA), monocyte TF mRNA, plasma coagulation factor VII (FVIIc), and thrombin-anti-thrombin complexes were higher in T2DM than in nondiabetic controls, indicating a chronic procoagulant state. Acutely normalizing hyperglycemia over 2–4 h resulted in a small (∼7%) but significant decline in TF-PCA with no further decline over 24 h. Raising insulin levels alone raised TF-PCA by 30%, whereas raising insulin and glucose levels together increased TF-PCA (by 80%), thrombin-anti-thrombin complexes, and prothrombin fragment 1.2. Plasma FVIIa and FVIIc declined with increases in TF-PCA. Conclusion: We conclude that the combination of hyperglycemia and hyperinsulinemia, common in poorly controlled patients with T2DM, contributes to a procoagulant state that may predispose these patients to acute cardiovascular events.

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Demethoxycurcumin inhibited human epithelia ovarian cancer cells’ growth via up-regulating miR-551a

Tumor Biology ◽

10.1177/1010428317694302 ◽

2017 ◽

Vol 39 (3) ◽

pp. 101042831769430 ◽

Cited By ~ 10

Author(s):

Zhenhua Du ◽

Xianqun Sha

Keyword(s):

Ovarian Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Ovarian Cancer Cells ◽

Natural Form ◽

Ovarian Cancer Cell Lines ◽

Induced Apoptosis ◽

Tumor Suppressive Function ◽

Cancer Tissues

Curcumin is a natural agent that has ability to dampen tumor cells’ growth. However, the natural form of curcumin is prone to degrade and unstable in vitro. Here, we demonstrated that demethoxycurcumin (a curcumin-related demethoxy compound) could inhibit cell proliferation and induce apoptosis of ovarian cancer cells. Moreover, IRS2/PI3K/Akt axis was inactivated in cells treated with demethoxycurcumin. Quantitative real-time reverse transcription polymerase chain reaction demonstrated that miR-551a was down-regulated in ovarian cancer tissues and ovarian cancer cell lines. Over-expression of miR-551a inhibited cell proliferation and induced apoptosis of ovarian cancer cells, whereas down-regulation of miR-551a exerted the opposite function. Luciferase assays confirmed that there was a binding site of miR-551a in IRS2, and we found that miR-551a exerted tumor-suppressive function by targeting IRS2 in ovarian cancer cells. Remarkably, miR-551a was up-regulated in the cells treated with demethoxycurcumin, and demethoxycurcumin suppressed IRS2 by restoration of miR-551a. In conclusion, demethoxycurcumin hindered ovarian cancer cells’ malignant progress via up-regulating miR-551a.

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