Effect of hypoxia on tissue factor pathway inhibitor expression in breast cancer

Cui, Xue; Tinholt, Mari; Stavik, Benedicte; Dahm, Anders Erik Astrup; Kanse, Sandip M.; Jin, Yang; Seidl, Sebastian; Sahlberg, Kristine Kleivi; Iversen, Nina; Skretting, Grethe; Sandset, Per Morten

doi:10.1111/jth.13206

Cited by 24 publications

(18 citation statements)

References 42 publications

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“…However, the classification may not be accurate, because some agents target more than one mechanism and it may be inappropriate to include them in a definite category. The targets and mechanisms of HIF inhibitors (Table 1) and some evaluated in clinical trials [Data were obtained from National Clinical Trial (https://clinicaltrials.gov)] are summarized 3031323334353637383940414243444546474849505152535455…”

Section: Hif Inhibitors For Cancer Therapymentioning

confidence: 99%

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Development of Inhibitors Targeting Hypoxia-Inducible Factor 1 and 2 for Cancer Therapy

2017

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Hypoxia is frequently observed in solid tumors and also one of the major obstacles for effective cancer therapies. Cancer cells take advantage of their ability to adapt hypoxia to initiate a special transcriptional program that renders them more aggressive biological behaviors. Hypoxia-inducible factors (HIFs) are the key factors that control hypoxia-inducible pathways by regulating the expression of a vast array of genes involved in cancer progression and treatment resistance. HIFs, mainly HIF-1 and -2, have become potential targets for developing novel cancer therapeutics. This article reviews the updated information in tumor HIF pathways, particularly recent advances in the development of HIF inhibitors. These inhibitors interfere with mRNA expression, protein synthesis, protein degradation and dimerization, DNA binding and transcriptional activity of HIF-1 and -2, or both. Despite efforts in the past two decades, no agents directly inhibiting HIFs have been approved for treating cancer patients. By analyzing results of the published reports, we put the perspectives at the end of the article. The therapeutic efficacy of HIF inhibitors may be improved if more efforts are devoted on developing agents that are able to simultaneously target HIF-1 and -2, increasing the penetrating capacity of HIF inhibitors, and selecting suitable patient subpopulations for clinical trials.

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Section: Hif Inhibitors For Cancer Therapymentioning

confidence: 99%

“…934593-90-5) was shown to reduce the accumulation and transcriptional activity of HIF-1α protein 47. A compound named PX-12 (1-methylpropyl 2-imidazolyl disulfide) inhibited HIF-1α protein accumulation by targeting thioredoxin-1 4849.…”

Section: Hif Inhibitors For Cancer Therapymentioning

confidence: 99%

Development of Inhibitors Targeting Hypoxia-Inducible Factor 1 and 2 for Cancer Therapy

2017

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“…In addition to the demonstrated role of the anticoagulant protein C (PC) pathway in controlling intravascular tumor dissemination (13;36-39), endothelial TF pathway inhibitor (TFPI) expression limits TF-dependent experimental metastasis (40). Tumor cell expression of TFPI is regulated by hypoxia inducible factor (HIF) 1α (41) and TFPI expression by tumor cells is correlated with improved outcome in breast cancer (42). Genetic polymorphisms associated with breast cancer furthermore show that traditional prothrombotic risk factors are not the sole determinant for tumor progression and that additional hemostatic components, i.e.…”

Section: Regulation Of Tf Activity and Procoagulant MV Releasementioning

confidence: 99%

Targeting clotting proteins in cancer therapy – progress and challenges

Ruf

Rothmeier

Graf

2016

Thrombosis Research

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Cancer-associated thrombosis remains a significant complication in the clinical management of cancer and interactions of the hemostatic system with cancer biology continue to be elucidated. Here, we review recent progress in our understanding of tissue factor (TF) regulation and procoagulant activation, TF signaling in cancer and immune cells, and the expanding roles of the coagulation system in stem cell niches and the tumor microenvironment. The extravascular functions of coagulant and anti-coagulant pathways have significant implications not only for tumor progression, but also for the selection of appropriate target specific anticoagulants in the therapy of cancer patients.

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“…The cells were cultured in DMEM supplemented with 10% FBS, 100 U/ml penicillin and 100 µg/ml streptomycin. Hypoxia was induced by exposing the cells to 150 µM CoCl 2 (Sigma-Aldrich; Merck KGaA) in DMEM with 0.5% FBS for 24 h ( 12 ). All cell cultures were maintained at 37°C in an atmosphere containing 5% CO 2 .…”

Section: Methodsmentioning

confidence: 99%

Oridonin inhibits VEGF‑A‑associated angiogenesis and epithelial‑mesenchymal transition of breast cancer in�vitro and in�vivo

Wang

Shen

et al. 2018

Oncol Lett

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Metastasis is the primary cause of mortality in patients with breast cancer and lacks effective therapeutic agents. Oridonin, an active diterpenoid compound isolated from Rabdosia rubescens, was identified to be the most potent anti-tumor ingredient. However, the molecular mechanisms responsible for its anti-metastatic effects remain unclear. In the present study, oridonin significantly suppressed the migration, invasion and adhesion of MDA-MB-231 and 4T1 breast cancer cells, and inhibited tube formation of human umbilical vein endothelial cells in a dose-dependent manner. The expression levels of epithelial-mesenchymal transition (EMT)-associated marker and the hypoxia inducible factor 1α (HIF-1α)/vascular endothelium growth factor (VEGF) signaling pathway mRNA and proteins were determined by reverse transcription-quantitative polymerase chain reaction and western blotting, respectively in vitro. The results demonstrated that oridonin effectively inhibited EMT as demonstrated by the significant increases in the expression levels of E-cadherin, and decreased expression of N-cadherin, Vimentin and Snail. In addition, oridonin exerted its anti-angiogenesis activity through significantly decreasing HIF-1α, VEGF-A and VEGF receptor-2 protein expression. Furthermore, oridonin was demonstrated to decrease the micro-vessel density as evidenced by the decreased expression of cluster of differentiation 31, a marker for neovasculature. In brief, oridonin inhibits tumor cell migration, invasion and adhesion, as well as tumor angiogenesis, which are mediated by suppressing EMT and the HIF-1α/VEGF signaling pathway. The results of the present study suggest that oridonin may be a promising anti-metastatic agent in breast cancer treatment.

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Effect of hypoxia on tissue factor pathway inhibitor expression in breast cancer

Cited by 24 publications

References 42 publications

Development of Inhibitors Targeting Hypoxia-Inducible Factor 1 and 2 for Cancer Therapy

Development of Inhibitors Targeting Hypoxia-Inducible Factor 1 and 2 for Cancer Therapy

Targeting clotting proteins in cancer therapy – progress and challenges

Oridonin inhibits VEGF‑A‑associated angiogenesis and epithelial‑mesenchymal transition of breast cancer in�vitro and in�vivo

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