Androgen receptor dampens tissue factor expression via nuclear factor‐κB and early growth response protein 1

Hoesel, Bastian; Mußbacher, Marion; Dikorman, B.; Salzmann, Manuel; Assinger, Alice; Hell, Lena; Thaler, Johannes; Basílio, José; Moser, Bernhard; Resch, Ulrike; Paar, Hannah; Mackman, Nigel; Schmid, Johannes A.

doi:10.1111/jth.13971

Cited by 6 publications

(6 citation statements)

References 35 publications

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“…Among these factors, tissue factor (TF) could interact with the coagulation factor FVII, triggering subsequent thrombin formation. ALK/ROS1 downstream NF-κB signaling might be involved in the expression of TF (52). Sen et al (53) found upregulation of TF in ALKfusion NSCLC patients.…”

Section: Discussionmentioning

confidence: 99%

High discrepancy in thrombotic events in non-small cell lung cancer patients with different genomic alterations

Liu¹,

Wang²,

Wu³

et al. 2021

Transl Lung Cancer Res

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Background: Acute complications, such as venous thromboembolism (VTE), are common in patients with advanced severe lung cancers. However, current VTE risk scores cannot adequately identify highrisk patients with non-small cell lung cancer (NSCLC). The study proposed to elucidated the incidence of thromboembolism (TE) in patients with different oncogenic aberrations and the impact of these aberrations on the efficacy of targeted therapy in patients with NSCLC.Methods: A systemic review was conducted in Web of Science, PubMed, Embase and the Cochrane Library to evaluate the incidence of TE in different molecular subtypes of NSCLC. Data from patients diagnosed of advanced NSCLC who harboring anaplastic lymphoma kinase (ALK) or ROS proto-oncogene 1 receptor tyrosine kinase (ROS1) rearrangements since 2016 to 2019 were also retrospectively collected.A meta-analysis with random-effects model, sensitivity analysis and publication bias were performed. The principal summary measure was incidence of thrombotic events in NSCLC patients. And the efficacy of tyrosine kinase inhibitor (TKI) therapy was compared between the two subgroups.Results: A total of 5,767 cases from 20 studies were included in the analysis of the incidence of thrombosis in patients with different oncogenic alterations. The pooled analysis showed a higher risk of thrombosis in ROS1fusion types (41%, 95% CI: 35-47%) and ALK-fusion types (30%, 95% CI: 24-37%) than in EGFR-mutation (12%, 95% CI: 8-17%), KRAS-mutation (25%, 95% CI: 13-50%), and wild-type (14%, 95% CI: 10-20%) cases. A high prevalence of thrombosis (ALK: 24.4%; ROS1: 32.6%) was observed in the Shanghai Pulmonary Hospital (SPH) cohort of 224 patients with ALK or ROS1 fusion. Furthermore, patients with embolism had significantly shorter progression-free survival (PFS) after TKI therapy than those without embolism, both in the ALK+ cohort (5.6 vs. 12.9 months, P<0.0001) and in the ROS1+ cohort (9.6 vs. 17.6 months, P=0.0481).Conclusions: NSCLC patients with ALK/ROS1 rearrangements are more likely to develop thrombosis than patients with other oncogenic alterations. Thrombosis may also be associated with an inferior response and PFS after TKI therapy.

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Section: Discussionmentioning

confidence: 99%

High discrepancy in thrombotic events in non-small cell lung cancer patients with different genomic alterations

Liu¹,

Wang²,

Wu³

et al. 2021

Transl Lung Cancer Res

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“…Given that androgen receptor dampens tissue factor, a pivotal mediator of coagulation and VTEs, expression via nuclear factor-kappa B (NF-κB) and early growth response protein 1, increased tissue factor expression is expected in androgen-deprived prostate cancer patients ( 27 ). In another in vitro study, androgen receptor-positive prostate cancer cell lines did not trigger platelet aggregation.…”

Section: Discussionmentioning

confidence: 99%

Association of Gonadotropin-Releasing Hormone Therapies With Venous Thromboembolic Events in Patients With Prostate Cancer: A National Cohort Study

Hong

Chen

et al. 2022

Front. Cardiovasc. Med.

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Although androgen deprivation therapy (ADT) has been proposed to be associated with a higher risk of venous thromboembolisms (VTEs), whether gonadotropin-releasing hormones (GnRHs), such as both agonists and antagonists, are also associated with VTEs remain unclear. Using the Taiwan Cancer Registry (TCR) linked with the National Health Insurance Research Database, we identified patients diagnosed with prostate cancer from 2008 to 2015. Patients who received GnRH were 1:1 propensity score matched with non-GnRH users by age and cancer stage at diagnosis and clinical stage. Cox regression analysis was applied to estimate the incidences of VTEs with death as a competing event at the 5-year follow-up. The VTE incidence among GnRH users was 1.13% compared with 0.98% among non-users. After adjusting with potential confounding factors, the risk of VTEs showed borderline statistical significance among GnRH users and non-users. Notably, in the subgroup analysis among patients receiving GnRH therapy, those younger than 70 years old or at an earlier stage (stage I/II) were at a higher risk of VTEs. Different from previous studies, our findings highlighted critical concerns regarding the cardiac safety of GnRH therapies in prostate cancer patients at a relatively younger age or at an earlier stage.

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“…We found 29 papers that used this antibody to measure human, mouse, rabbit and canine TF by a variety of methods, including 15 that used the antibody for western blotting (Table S1). 33‐61 Importantly, Abcam evaluated the ability of the antibody to detect human TF in wild‐type and KO cell lines by western blotting 62 . Based on the data they obtained, they recently withdrew ab151748 and stated that “after evaluation, using a HAP1 knockout cell line, ab151748 was not shown to react specifically with the target protein and has therefore been discontinued.” We confirmed that this antibody does not detect mouse TF by western blotting but rather a nonspecific band.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of different commercial antibodies for their ability to detect human and mouse tissue factor by western blotting

Rosell

Moser

Hisada

et al. 2020

Research and Practice in Thrombosis and Haemostasis

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Background Western blotting is used to measure protein expression in cells and tissues. Appropriate interpretation of resulting data is contingent upon antibody validation. Objectives We assessed several commercial anti‐human and anti‐mouse tissue factor (TF) antibodies for their ability to detect TF by western blotting. Material and Methods We used human pancreatic cancer cell lines expressing different levels of TF and a mouse pancreatic cancer cell line expressing TF with a matched knockout derivative. Results Human and mouse TF protein detected by western blotting correlated with levels of TF mRNA in these cell lines. The apparent molecular weight of TF is increased by N‐linked glycosylation and, as expected, deglycosylation decreased the size of TF based on western blotting. We found that four commercial anti‐human TF antibodies detected TF in a TF‐positive cell line HPAF‐II whereas no signal was observed in a TF‐negative cell line MIA PaCa‐2. More variability was observed in detecting mouse TF. Two anti‐mouse TF antibodies detected mouse TF in a TF‐positive cell line and no signal was observed in a TF knockout cell line. However, a third anti‐mouse TF antibody detected a nonspecific protein in both the mouse TF‐positive and TF‐negative cell lines. Two anti‐human TF antibodies that are claimed to cross react with mouse TF either recognized a nonspecific band or did not detect mouse TF. Discussion Our results indicate that there is a range in quality of commercial anti‐TF antibodies. Conclusion We recommend that all commercial antibodies should be validated to ensure that they detect TF.

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Androgen receptor dampens tissue factor expression via nuclear factor‐κB and early growth response protein 1

Cited by 6 publications

References 35 publications

High discrepancy in thrombotic events in non-small cell lung cancer patients with different genomic alterations

High discrepancy in thrombotic events in non-small cell lung cancer patients with different genomic alterations

Association of Gonadotropin-Releasing Hormone Therapies With Venous Thromboembolic Events in Patients With Prostate Cancer: A National Cohort Study

Evaluation of different commercial antibodies for their ability to detect human and mouse tissue factor by western blotting

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