Molecular cloning of the cDNA for human tissue factor

Konigsberg, William H.; Nemerson, Yale

doi:10.1016/0092-8674(88)90399-6

Cited by 20 publications

(21 citation statements)

References 2 publications

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“…TF is a cell membrane-bound glycoprotein (MW 46 kDa) comprised of a hydrophilic extracellular domain, a membrane-spanning hydrophobic domain, and a cytoplasmic tail of 21 residues [98, 99]. Biological activity of the mature protein requires posttranslational modification to include carbohydrate moieties [100–102].…”

Section: Tissue Factormentioning

confidence: 99%

Endometriosis, Angiogenesis and Tissue Factor

Krikun

2012

Scientifica

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Tissue factor (TF), is a cellular receptor that binds the factor VII/VIIa to initiate the blood coagulation cascade. In addition to its role as the initiator of the hemostatic cascade, TF is known to be involved in angiogenesis via intracellular signaling that utilizes the protease activated receptor-2 (PAR-2). We now review the physiologic expression of TF in the endometrium and its altered expression in multiple cell types derived from eutopic and ectopic endometrium from women with endometriosis compared with normal endometrium. Our findings suggest that TF might be an ideal target for therapeutic intervention in endometriosis. We have employed a novel immunoconjugate molecule known as Icon and were able to eradicate endometrial lesions in a mouse model of endometriosis without affecting fertility. These findings have major implications for potential treatment in humans.

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Section: Tissue Factormentioning

confidence: 99%

Endometriosis, Angiogenesis and Tissue Factor

Krikun

2012

Scientifica

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“…TF is a transmembrane receptor [36][37][38][39] that forms an exceptionally strong and specific complex with its natural ligand fVII [40][41][42], and this interaction is the initial step of the coagulation pathway [38]. Research has shown that TF is expressed on endothelial cells of pathologic capillary blood vessels associated with solid tumors [29,31,33,[43][44][45], wMD [46,47] and endometriosis [48], but TF is not expressed on the VECs of normal blood vessels [31,33,43,[49][50][51].…”

Section: Introductionmentioning

confidence: 99%

Effective Treatment of Human Lung Cancer by Targeting Tissue Factor with a Factor VII-Targeted Photodynamic Therapy

Cheng¹,

Xu²,

Duanmu³

et al. 2011

CCDT

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Lung cancer is the leading cause of cancer death. Conventional photodynamic therapy (PDT) using a nontargeted photosensitizer (ntPDT) is a treatment option for central- and peripheral-type early-stage lung cancer. However, ntPDT can cause severe side effects for normal tissue due to its non-selective distribution. To improve the selectivity and effectiveness of ntPDT for human lung cancer, we hypothesized that tissue factor would be a common yet specific biomarker and a potential therapeutic target for both lung cancer cells and lung tumor vascular endothelial cells in factor VII-targeted PDT (fVII-tPDT), which uses the fVII-Sn(IV) chlorin e6 conjugate for the treatment of human lung cancer. We first identified that tissue factor is indeed expressed on the human non-small cell lung cancer (NSCLC) lines A549 and H460 as well as on tumor vascular endothelial cells of A549 tumor xenografts from nude mice, but it is not expressed by vascular endothelial cells in healthy mouse organs including the lungs. We then demonstrated that fVII-targeting in fVII-tPDT significantly enhanced (up to 25-fold) the in vitro effect of ntPDT on the destruction of A549 and H460 lung cancer cells via the rapid induction of apoptosis and necrosis. We further demonstrated that in vivo administration of fVIItPDT significantly inhibited or eliminated subcutaneous A549 and H460 tumor xenografts in an athymic nude (ATN) mouse model without any obvious side effects. We conclude that fVII-tPDT is effective and safe for the treatment of human lung cancer in preclinical studies and that this methodology holds therapeutic potential for lung cancer patients.

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“…Based on the in vivo observation of TF expression on tumor vascular endothelial cells in breast cancer tissues from patients [4] and some mouse models of human tumor xenografts [5–7], we have begun developing such an approach using tissue factor (TF), a 47-kDa membrane-bound receptor [4, 8–11], as the target molecule on angiogenic VECs. To assemble this TF-directed treatment, we used, as the starting molecule, the principal ligand of TF, factor VII (fVII) [12].…”

Section: Introductionmentioning

confidence: 99%

Tissue factor is an angiogenic-specific receptor for factor VII-targeted immunotherapy and photodynamic therapy

Cheng

et al. 2016

Angiogenesis

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Identification of target molecules specific for angiogenic vascular endothelial cells (VEC), the inner layer of pathological neovasculature, is critical for discovery and development of neovascular-targeting therapy for angiogenesis-dependent human diseases, notably cancer, macular degeneration and endometriosis, in which vascular endothelial growth factor (VEGF) plays a central pathophysiological role. Using VEGF-stimulated vascular endothelial cells (VECs) isolated from microvessels, venous and arterial blood vessels as in vitro angiogenic models and unstimulated VECs as a quiescent VEC model, we examined the expression of tissue factor (TF), a membrane-bound receptor on the angiogenic VEC models compared with quiescent VEC controls. We found that TF is specifically expressed on angiogenic VECs in a time-dependent manner in microvessels, venous and arterial vessels. TF-targeted therapeutic agents, including factor VII (fVII)-IgG1 Fc and fVII-conjugated photosensitizer, can selectively bind angiogenic VECs, but not the quiescent VECs. Moreover, fVII-targeted photodynamic therapy can selectively and completely eradicate angiogenic VECs. We conclude that TF is an angiogenic-specific receptor and the target molecule for fVII-targeted therapeutics. This study supports clinical trials of TF-targeted therapeutics for the treatment of angiogenesis-dependent diseases such as cancer, macular degeneration and endometriosis.

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Molecular cloning of the cDNA for human tissue factor

Cited by 20 publications

References 2 publications

Endometriosis, Angiogenesis and Tissue Factor

Endometriosis, Angiogenesis and Tissue Factor

Effective Treatment of Human Lung Cancer by Targeting Tissue Factor with a Factor VII-Targeted Photodynamic Therapy

Tissue factor is an angiogenic-specific receptor for factor VII-targeted immunotherapy and photodynamic therapy

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