Increased expression of tissue factor and protease-activated receptor-1 does not correlate with thrombosis in human lung adenocarcinoma

Meis, Ernesto de; Azambuja, Denize; Ayres-Silva, Jackline de Paula; Zamboni, Mauro; Pinheiro, Vera R.; Levy, RA; Monteiro, Robson Q.

doi:10.1590/s0100-879x2010007500017

Cited by 19 publications

(19 citation statements)

References 22 publications

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“…57,76,77 Furthermore, associations have been found with invasiveness in breast cancer 15 and melanomas, 15,76 high clinical staging in lung, 13,14,40,57 pancreas, 62,63 colorectal, 65,66 and prostate cancer, 74 and metastases in cancers of breast, 53 lung, 56 esophagus, 59 gastric, 60 hepatic, 61 pancreatic, 63 and colorectal 67 tissues. Other studies, however, could not find such associations between flTF expression and unfavorable pathologic and clinical parameters 54,55,68,76,77,81 ; this may partially be because of differences in patient populations, population size, and detection techniques for flTF.…”

Section: Tf Isoforms In Human Cancermentioning

confidence: 99%

The relationship between tissue factor and cancer progression: insights from bench and bedside

Berg¹,

Osanto

Reitsma³

et al. 2012

Blood

304

243

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It is now widely recognized that a strong correlation exists between cancer and aberrant hemostasis. Patients with various types of cancers, including pancreatic, colorectal, and gastric cancer, often develop thrombosis, a phenomenon commonly referred to as Trousseau syndrome. Reciprocally, components from the coagulation cascade also influence cancer progression. The primary initiator of coagulation, the transmembrane receptor tissue factor (TF), has gained considerable attention as a determinant of tumor progression. On complex formation with its ligand, coagulation factor VIIa, TF influences protease-activated receptor-dependent tumor cell behavior, and regulates integrin function, which facilitate tumor angiogenesis both in vitro and in mouse models. Furthermore, evidence exists that an alternatively spliced isoform of TF also affects tumor growth and tumor angiogenesis. In patient material, TF expression and TF cytoplasmic domain phosphorylation correlate with disease outcome in many, but not in all, cancer subtypes, suggesting that TFdependent signal transduction events are a potential target for therapeutic intervention in selected types of cancer. In this review, we summarize our current understanding of the role of TF in tumor growth and metastasis, and speculate on anticancer therapy by targeting TF. (Blood. 2012; 119(4):924-932) IntroductionAfter Trousseau's description of thrombophlebitis as a complication of pancreatic cancer in the 19th century, the notion that increased expression of tissue factor (TF) underlies the relation between coagulation and cancer has become generally accepted. Full-length TF (flTF) is a 47-kDa membrane-bound glycoprotein that is present on subendothelial cells. 1 In the classic concept of coagulation, it is thought that endothelial disruption leads to exposure of flTF to the bloodstream. Exposed flTF can bind to its natural ligand factor VII (FVII), which then becomes activated FVII (FVIIa). The thus formed flTF/FVIIa complex converts factor X (FX) to factor Xa (FXa), and FXa in turn activates prothrombin leading to formation of thrombin (factor IIa). Thrombin subsequently activates platelets and converts fibrinogen into fibrin, 2 essential components of a stable hemostatic plug. 1 The primary function of subendothelial flTF is to serve as a hemostatic envelope surrounding the vasculature. However, under certain conditions, the expression of flTF is induced in monocytes and endothelial cells. flTF is also often expressed on cancer cells and the tumor vasculature, 2 and flTF-bearing microparticles can become shed by these cells. 3 These flTF-bearing microparticles are important contributors to the thrombotic phenotype in cancer patients. 3 The flTF/FVIIa complex also influences pathways that do not lead to blood coagulation, but rather activate cell-bound proteaseactivated receptors (PARs) that are of importance during the inflammatory and angiogenic response to injury. 4 Furthermore, a soluble variant of flTF, known as alternatively spliced TF (asTF), stimulates angiogen...

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Section: Tf Isoforms In Human Cancermentioning

confidence: 99%

The relationship between tissue factor and cancer progression: insights from bench and bedside

Berg¹,

Osanto

Reitsma³

et al. 2012

Blood

304

243

View full text Add to dashboard Cite

show abstract

“…However, not all studies confirm a link between TF and VTE. In a prospective study on non‐small cell lung carcinoma (n = 39), TF expression did not associate with increased risk of VTE 24. Similarly, in a study by Thaler et al., TF expression in brain tumors did not associate with increased VTE events 25.…”

Section: Tissue Factormentioning

confidence: 70%

Cancer‐associated thrombosis: The search for the holy grail continues

Ünlü

Versteeg

2018

Research and Practice in Thrombosis and Haemostasis

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Cancer patients have an increased risk of developing venous thromboembolism (VTE), a condition that is associated with increased morbidity and mortality. Although risk assessment tools have been developed, it is still very challenging to predict which cancer patients will suffer from VTE. The scope of this review is to summarize and discuss studies focusing on the link between genetic alterations and risk of cancer‐associated thrombosis (CAT). Thus far, classical risk factors that contribute to VTE have been tried as risk factors of CAT, with low success. In support, hypercoagulant plasma profiles in patients with CAT differ from those with only VTE, indicating other risk factors that contribute to VTE in cancer. As germline mutations do not significantly contribute to elevated risk of VTE, somatic mutations in tumors may significantly associate with and contribute to CAT. As it is very time‐consuming to investigate each and every mutation, an unbiased approach is warranted. In this light we discuss our own recent unbiased proof‐of‐principle study using RNA sequencing in isolated colorectal cancer cells. Our work has uncovered candidate genes that associate with VTE in colorectal cancer, and these gene profiles associated with VTE more significantly than classical parameters such as platelet counts, D‐dimer, and P‐selectin levels. Genes associated with VTE could be linked to pathways being involved in coagulation, inflammation and methionine degradation. We conclude that tumor cell‐specific gene expression profiles and/or mutational status has superior potential as predictors of VTE in cancer patients.

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“…However, these findings were not specifically associated with outcome. 25 PAR1 expression was found in melanoma cells and was associated with Breslow thickness, ulceration and recurrence. We predicted that both MVD and PAR1 could be used as adjuncts to Breslow thickness and ulceration as prognostic indicators for melanoma because they appeared to give independent information for all thicknesses 31.…”

Section: Discussionmentioning

confidence: 98%

Effect of thrombin receptor expression on microvessel endothelial cells, and survival by coagulation state in oesophageal squamous cell carcinoma

Shao

et al. 2012

J Clin Pathol

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Increased expression of tissue factor and protease-activated receptor-1 does not correlate with thrombosis in human lung adenocarcinoma

Cited by 19 publications

References 22 publications

The relationship between tissue factor and cancer progression: insights from bench and bedside

The relationship between tissue factor and cancer progression: insights from bench and bedside

Cancer‐associated thrombosis: The search for the holy grail continues

Effect of thrombin receptor expression on microvessel endothelial cells, and survival by coagulation state in oesophageal squamous cell carcinoma

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