Association of tissue-factor upregulation in squamous-cell carcinoma of the lung with increased tissue factor in circulating blood

Rauch, Ursula; Antoniak, Silvio; Boots, Miriam; Schulze, Karsten; Goldin-Lang, Petra; Stein, Harald; Schultheiss, Heinz‐Peter; Coupland, Sarah E.

doi:10.1016/s1470-2045(05)70099-1

Cited by 32 publications

(22 citation statements)

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“…Interestingly, in a panel of 10 cervical tumors, we found that nine out of 10 tumors contained asTF at levels in the range within which asTF is pro-angiogenic, rendering asTF a potential key player in tumor angiogenesis. In agreement, asTF is expressed in pancreatic cell lines (18), squamous cell carcinoma of the lung (27), and advanced stages of non-small cell lung cancer (19); asTF appears to drive tumor growth in xenograft models (20). It remains controversial whether asTF always displays coagulant activity and can be effectively secreted (16).…”

Section: Discussionmentioning

confidence: 92%

Alternatively spliced tissue factor induces angiogenesis through integrin ligation

Berg¹,

Hengel²,

Myers³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

135

176

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The initiator of coagulation, full-length tissue factor (flTF), in complex with factor VIIa, influences angiogenesis through PAR-2. Recently, an alternatively spliced variant of TF (asTF) was discovered, in which part of the TF extracellular domain, the transmembrane, and cytoplasmic domains are replaced by a unique C terminus. Subcutaneous tumors produced by asTF-secreting cells revealed increased angiogenesis, but it remained unclear if and how angiogenesis is regulated by asTF. Here, we show that asTF enhances angiogenesis in matrigel plugs in mice, whereas a soluble form of flTF only modestly enhances angiogenesis. asTF dose-dependently upregulates angiogenesis ex vivo independent of either PAR-2 or VIIa. Rather, asTF was found to ligate integrins, resulting in downstream signaling. asTF-␣V␤3 integrin interaction induces endothelial cell migration, whereas asTFdependent formation of capillaries in vitro is dependent on ␣6␤1 integrin. Finally, asTF-dependent aortic sprouting is sensitive to ␤1 and ␤3 integrin blockade and a TF-antibody that disrupts asTFintegrin interaction. We conclude that asTF, unlike flTF, does not affect angiogenesis via PAR-dependent pathways but relies on integrin ligation. These findings indicate that asTF may serve as a target to prevent pathological angiogenesis.cancer ͉ coagulation ͉ endothelial cells ͉ integrins

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Section: Discussionmentioning

confidence: 92%

Alternatively spliced tissue factor induces angiogenesis through integrin ligation

Berg¹,

Hengel²,

Myers³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

135

176

View full text Add to dashboard Cite

show abstract

“…Increased levels of circulating TF are commonly detected in patients with advanced cancer [45,47,[50][51][52][53][54] and copious amounts of TF antigen are often detectable on the surfaces of cancer cells themselves, as well as in association with various elements of tumour stroma, in particular by tumour-infiltrating macrophages and some angiogenic endothelial cells [92][93][94][95] . Indeed, cancer cells may express as much as a 1,000-fold higher levels of TF than their corresponding normal cells [96] .…”

Section: The Link Between Tissue Factor and Malignancymentioning

confidence: 99%

Tissue Factor and Cancer

Milsom

Rak

2007

Pathophysiol Haemos Thromb

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Tissue factor (TF), the key regulator of haemostasis and angiogenesis, is also involved in the pathology of several diseases, including cardiovascular, inflammatory and neoplastic conditions. In the latter, TF is upregulated by cancer cells, as well as by certain host cells, and it is the interactions between these distinct pools of TF-expressing cells that likely influence tumour progression in several ways. Furthermore, the release of TF microparticles into the circulation is thought to contribute to the systemic coagulopathies commonly observed in cancer patients. The direct regulation of TF by oncogenic events has provided a plausible explanation for the relatively common overexpression of TF in various cancers and its involvement in tumour growth, angiogenesis, metastasis and coagulopathy. However, this constitutive influence is modified by the tumour microenvironment, cellular interactions and host factors rendering TF expression patterns complex and heterogeneous. It appears that in many biological contexts TF plays a central role in disease progression and thereby potentially constitutes an attractive therapeutic target, especially in scenarios where the risk of bleeding can be avoided by selecting appropriate medications, refined dosing or by targeting the signalling component of TF activity. The efficacy and safety of such approaches still awaits clinical verification.

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“…TF is expressed in human lung cancer cell lines (Keller et al, 2001;Minamiya et al, 2004;Rauch et al, 2005;Salge et al, 2001;Zacharski et al, 1983) as well as in about 40-80% of human lung tumor tissues from patients worldwide (Koomagi and Volm, 1998;Sawada et al, 1999;Shoji et al, 1998;Wang et al, 2005). Shoji et al (Shoji et al, 1998) reported that TF expression on stromal macrophage and vascular endothelial cells was detected in 76% (19 out of 25) of lung cancer patients, while lung cancer TF expression was detected in only 28% of these patients.…”

Section: Tf In 40-80% Of Lung Cancermentioning

confidence: 99%

Factor VII-Targeted Photodynamic Therapy for Breast Cancer and Its Therapeutic Potential for Other Solid Cancers and Leukemia

Hu¹

2011

Breast Cancer - Current and Alternative Therapeutic Modalities

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Association of tissue-factor upregulation in squamous-cell carcinoma of the lung with increased tissue factor in circulating blood

Cited by 32 publications

References 0 publications

Alternatively spliced tissue factor induces angiogenesis through integrin ligation

Alternatively spliced tissue factor induces angiogenesis through integrin ligation

Tissue Factor and Cancer

Factor VII-Targeted Photodynamic Therapy for Breast Cancer and Its Therapeutic Potential for Other Solid Cancers and Leukemia

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