Hematophagy and Inhibition of the Extrinsic and Intrinsic Tenase Complexes

Monteiro, Robson Q.; Andersen, John F.; Francischetti, Ivo M.B.

doi:10.1007/978-90-481-9295-3_14

Cited by 2 publications

(3 citation statements)

References 79 publications

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“…We further demonstrated that ixolaris blocks PAR2-mediated signalling in human breast tumour cells, thus accounting for the reduced production of pro-tumoural molecules [129]. NAPc2 is a TF/FVIIa inhibitor characterized from the haematophagous nematode Ancylostoma caninum [130]. It displays an anticoagulant mechanism of action that is similar to ixolaris and it inhibits primary tumour growth and metastasis in animal models [131].…”

Section: Therapies Targeting Blood Coagulation-related Proteinsmentioning

confidence: 99%

Activation of blood coagulation in cancer: implications for tumour progression

2013

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Several studies have suggested a role for blood coagulation proteins in tumour progression. Herein, we discuss (1) the activation of the blood clotting cascade in the tumour microenvironment and its impact on primary tumour growth; (2) the intravascular activation of blood coagulation and its impact on tumour metastasis and cancer-associated thrombosis; and (3) antitumour therapies that target blood-coagulation-associated proteins. Expression levels of the clotting initiator protein TF (tissue factor) have been correlated with tumour cell aggressiveness. Simultaneous TF expression and PS (phosphatidylserine) exposure by tumour cells promote the extravascular activation of blood coagulation. The generation of blood coagulation enzymes in the tumour microenvironment may trigger the activation of PARs (protease-activated receptors). In particular, PAR1 and PAR2 have been associated with many aspects of tumour biology. The procoagulant activity of circulating tumour cells favours metastasis, whereas the release of TF-bearing MVs (microvesicles) into the circulation has been correlated with cancer-associated thrombosis. Given the role of coagulation proteins in tumour progression, it has been proposed that they could be targets for the development of new antitumour therapies.

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Section: Therapies Targeting Blood Coagulation-related Proteinsmentioning

confidence: 99%

Activation of blood coagulation in cancer: implications for tumour progression

2013

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“…The FIX/ FIXa binding occurs through its B-C and E-F strands as well as its C-terminus [94]. (For details, see [91]).…”

Section: Intrinsic Tenase Complex Inhibitorsmentioning

confidence: 99%

“…In contrast, AceAP1 uses FXa as a scaffold by binding to both its active site and exosite, and forms a quaternary complex with the FVIIa‐TF complex [87,88]. (For details, see [91]).…”

Section: Anticoagulant Proteins From Haematophagous Animalsmentioning

confidence: 99%

Toxins in thrombosis and haemostasis: potential beyond imagination

Kini

2011

Journal of Thrombosis and Haemostasis

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Summary. Exogenous factors isolated from venoms of snakes and saliva of haematophagous animals that affect thrombosis and haemostasis have contributed significantly to the development of diagnostic agents, research tools and life-saving drugs. Here, I discuss recent advances in the discovery, structural and functional characterisation, and mechanism of action of new procoagulant and anti-haemostatic proteins. In nature, these factors have evolved to target crucial ÔbottlenecksÕ in the coagulation cascade and platelet aggregation. Several simple protein scaffolds are used to target a wide variety of target proteins and receptors exhibiting functional divergence. Different protein scaffolds have also evolved to target identical, physiologically relevant key enzymes or receptors exhibiting functional convergence. At times, exogenous factors bind to the same target protein, but at distinct sites, to differentially attenuate their functions exhibiting mechanistic divergence within the same family of proteins. The structure-function relationships of these factors are subtle and complicated but represent an exciting challenge. These studies provide ample opportunities to design highly specific and precise ligands to achieve desired biological target function. Although only a small number of them have been characterised to date, the molecular and mechanical diversities of these exogenous factors and their contributions to understanding molecular and cellular events in thrombosis and haemostasis as well as developing diagnostic and research tools and therapeutic agents, is outstanding. Based on the current status, I have attempted to identify future potential and prospects in this area of research.

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Hematophagy and Inhibition of the Extrinsic and Intrinsic Tenase Complexes

Cited by 2 publications

References 79 publications

Activation of blood coagulation in cancer: implications for tumour progression

Activation of blood coagulation in cancer: implications for tumour progression

Toxins in thrombosis and haemostasis: potential beyond imagination

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