Expression of tissue factor pathway inhibitor (TFPI) in human breast and colon cancer tissue

Sierko, Ewa; Wojtukiewicz, Marek Z.; Zimnoch, L; Kisiel, Walter

doi:10.1160/th09-06-0416

Cited by 43 publications

(46 citation statements)

References 39 publications

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“…However, more recent evidence indicates an additional role of TFPI in cancer. Several cancer tissues and cell lines have been shown to express TFPI [14], [15], and TFPI treatment has been reported to reduce tumor growth and metastasis in vivo [16], [17]. We recently reported that overexpression of TFPIα or TFPIβ in SK-BR-3 breast cancer cells resulted in pro-apoptotic and anti-proliferative effects of either isoform in vitro [18], but the mechanism behind the effect of TFPI is poorly understood.…”

Section: Introductionmentioning

confidence: 99%

TFPI Alpha and Beta Regulate mRNAs and microRNAs Involved in Cancer Biology and in the Immune System in Breast Cancer Cells

et al. 2012

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Emerging evidence indicate a new role of TFPI in cancer biology. We recently reported that both isoforms of TFPI induced apoptosis and inhibited proliferation of cancer cells. The signaling pathway(s) mediating the effects of TFPI is, however, presently still unclear. Our goal was to further investigate the cellular processes affected by TFPI and to get insight into the molecular mechanisms involved in the effects of TFPI, using a global gene expression study approach. TFPIα or TFPIβ cDNA were transfected into SK-BR-3 breast cancer cells for stable overexpression. Global mRNA and microRNA (miRNA) expressions were measured and functional annotation of the differentially expressed genes and miRNAs according to gene ontology terms was conducted. Selected results were validated using qRT-PCR and Western blot. A total of 242 and 801 mRNA transcripts and 120 and 46 miRNAs were differentially expressed in cells overexpressing TFPIα or TFPIβ, respectively. Overexpression of either isoform significantly affected the expression of genes involved in cell development (apoptosis, cell movement, migration, invasion, colony formation, growth, and adhesion) and immune response. Network analyses revealed biological interactions between these genes and implied that several of the genes may be involved in both processes. The expression profiles also correlated significantly with clinical phenotype and outcome. Functional cluster analyses indicated altered activity of the epidermal growth factor receptor, small GTPases, and the NF-κB and JAK/STAT cascades when TFPI was overexpressed, and increased activity of the transcription factors NF-κB and Elk-1 and phospho-Akt levels was observed. Integrated mRNA-miRNA analyses showed that 19% and 32% of the differentially expressed genes in cells overexpressing TFPIα or TFPIβ, respectively, may have been regulated by miRNAs. Overexpression of TFPI in breast cancer cells affected the expression of mRNAs and miRNAs involved in processes facilitating cancer cell growth and immunologic response, possibly by signal transduction involving the EGFR pathway.

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Section: Introductionmentioning

confidence: 99%

TFPI Alpha and Beta Regulate mRNAs and microRNAs Involved in Cancer Biology and in the Immune System in Breast Cancer Cells

et al. 2012

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“…In ABC IHC technique the examined antigens were visualized as dark brown reaction products. The expression level of the receptors was measured using semiquantitative scale by Remmale and Stegner in our own modification [25]. Numerical results were grouped by the percentage of stained cells (A) and intensiveness of this staining (B).…”

Section: Methodsmentioning

confidence: 99%

Granulocyte-Colony Stimulating Factor Receptor, Tissue Factor, and VEGF-R Bound VEGF in Human Breast Cancer In Loco

et al. 2016

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“…TFPI-2 is highly expressed in the placenta, but is also synthesized in various normal tissues, including the endothelial cells of various blood vessels [66] . Previous studies have shown that breast cancer tissues may also synthesize TFPI-1 [67] and TFPI-2 [66] , and TFPI-1 expression levels were correlated with disease malignancy. In keeping with this observation, multiple breast cancer cell lines also express TFPIα and TFPIβ [68] .…”

Section: Tissue Factor Pathway Inhibitors: Negative Regulators Of Tf-mentioning

confidence: 99%

Breast cancer phenotypes regulated by tissue factor-factor VII pathway: Possible therapeutic targets

Koizume

Miyagi

2014

WJCO

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Breast cancer is a leading cause of cancer death in women, worldwide. Fortunately, breast cancer is relatively chemosensitive, with recent advances leading to the development of effective therapeutic strategies, significantly increasing disease cure rate. However, disease recurrence and treatment of cases lacking therapeutic molecular targets, such as epidermal growth factor receptor 2 and hormone receptors, referred to as triple-negative breast cancers, still pose major hurdles in the treatment of breast cancer. Thus, novel therapeutic approaches to treat aggressive breast cancers are essential. Blood coagulation factor VII (fVII) is produced in the liver and secreted into the blood stream. Tissue factor (TF), the cellular receptor for fVII, is an integral membrane protein that plays key roles in the extrinsic coagulation cascade. TF is overexpressed in breast cancer tissues. The TF-fVII complex may be formed in the absence of injury, because fVII potentially exists in the tissue fluid within cancer tissues. The active form of this complex (TF-fVIIa) may stimulate the expression of numerous malignant phenotypes in breast cancer cells. Thus, the TF-fVII pathway is a potentially attractive target for breast cancer treatment. To date, a number of studies investigating the mechanisms by which TF-fVII signaling contributes to breast cancer progression, have been conducted. In this review, we summarize the mechanisms controlling TF and fVII synthesis and regulation in breast cancer cells. Our current understanding of the TF-fVII pathway as a mediator of breast cancer progression will be also described. Finally, we will discuss how this knowledge can be applied to the design of future therapeutic strategies. Key words: Breast cancer; Blood coagulation; Tissue factor; Coagulation factor VII; Gene regulation; Therapeutic strategy Core tip: Breast cancer is a worldwide problem. Difficulties with treating the disease and its recurrence persist due, in part, to a lack of therapeutic molecular targets. Blood coagulation factor VII (fVII) is generally produced in the liver. Tissue factor (TF), the cellular receptor for fVII, is an integral membrane protein that plays key roles in the extrinsic coagulation cascade. Formation of the TF-fVII complex causes contributes to the malignant phenotype of breast cancer cells. In this review, we summarize the breast cancer biology associated with the TF-fVII pathway. Further, we will discuss how these mechanisms can be targeted as therapeutics for this aggressive disease.Koizume S, Miyagi Y. Breast cancer phenotypes regulated by tissue factor-factor VII pathway: Possible therapeutic targets.

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Expression of tissue factor pathway inhibitor (TFPI) in human breast and colon cancer tissue

Cited by 43 publications

References 39 publications

TFPI Alpha and Beta Regulate mRNAs and microRNAs Involved in Cancer Biology and in the Immune System in Breast Cancer Cells

TFPI Alpha and Beta Regulate mRNAs and microRNAs Involved in Cancer Biology and in the Immune System in Breast Cancer Cells

Granulocyte-Colony Stimulating Factor Receptor, Tissue Factor, and VEGF-R Bound VEGF in Human Breast Cancer In Loco

Breast cancer phenotypes regulated by tissue factor-factor VII pathway: Possible therapeutic targets

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