Use of Ixolaris as a Diagnostic Tool for Cancer Models

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Sergio Augusto Lopes de Souza Thiago Barboza Bianca Gutfilen Robson de Queiroz Monteiro

Abstract

Ixolaris is a tick salivary protein that binds to Factor Xa or Factor X as a scaffold for inhibition of the Tissue Factor (TF)/Factor VIIa (FVIIa). TF is not normally expressed in cells that are in direct contact with blood. However, TF is abnormally expressed under several pathological conditions, including inflammation, infectious diseases and cancer. It is known for decades that TF is a risk factor for metastasis, and in mouse models, TF drives metastasis in a coagulation-dependent manner. For these reasons, TF has recently been described as a potential target that can be exploited to image aggressive tumors. Ixolaris has been succcesfully used to treat some pre-clinical cancer models. It also has been shown its’ radiolabeling for diagnostic and therapeutic purposes. The aim of this article is to show that Ixolaris could be an interesting tool to diagnose cancer, and also treat it in a near future. Some key findings presented here are that TF has recently been described as a potential target that can be exploited to image aggressive tumors, once it is often associated with migration, invasion, proliferation, metastasis, the inhibition of apoptosis and the production of several pro-aggressive factors.

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How to Cite
SOUZA, Sergio Augusto Lopes de et al. Use of Ixolaris as a Diagnostic Tool for Cancer Models. Medical Research Archives, [S.l.], v. 10, n. 5, june 2022. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/2779>. Date accessed: 25 june 2022. doi: https://doi.org/10.18103/mra.v10i5.2779.
Section
Research Articles

References

1. MONTEIRO RQ, REZAIE AR, RIBEIRO JMC, FRANCISCHETTI IMB. Ixolaris: a Factor Xa heparin-binding exosite inhibitor. Published online 2005:7.
2. Monteiro RQ. Targeting exosites on blood coagulation proteases. An Acad Bras Ciênc. 2005;77(2):275-280. doi:10.1590/S0001-37652005000200007
3. Monteiro RQ, Rezaie AR, Bae JS, Calvo E, Andersen JF, Francischetti IMB. Ixolaris binding to factor X reveals a precursor state of factor Xa heparin-binding exosite. Protein Science. 2007;17(1):146-153. doi:10.1110/ps.073016308
4. Francischetti IMB. Ixolaris, a novel recombinant tissue factor pathway inhibitor (TFPI) from the salivary gland of the tick, Ixodes scapularis: identification of factor X and factor Xa as scaffolds for the inhibition of factor VIIa/tissue factor complex. Blood. 2002;99(10):3602-3612. doi:10.1182/blood-2001-12-0237
5. Milić D, Veprintsev DB. Large-scale production and protein engineering of G protein-coupled receptors for structural studies. Front Pharmacol. 2015;6. doi:10.3389/fphar.2015.00066
6. De Paula VS, Silva FHS, Francischetti IMB, Monteiro RQ, Valente AP. Recombinant expression of Ixolaris, a Kunitz-type inhibitor from the tick salivary gland, for NMR studies. Protein Expression and Purification. 2017;139:49-56. doi:10.1016/j.pep.2017.07.012
7. Wahed A, ed. Hematology and Coagulation. Elsevier; 2019.
8. Lima LG, Monteiro RQ. Activation of blood coagulation in cancer: implications for tumour progression. Bioscience Reports. 2013;33(5):e00064. doi:10.1042/BSR20130057
9. Furie B. Thrombus formation in vivo. Journal of Clinical Investigation. 2005;115(12):3355-3362. doi:10.1172/JCI26987
10. Engelmann B. Initiation of coagulation by tissue factor carriers in blood. Blood Cells, Molecules, and Diseases. 2006;36(2):188-190. doi:10.1016/j.bcmd.2005.12.020
11. Kretz CA, Vaezzadeh N, Gross PL. Tissue Factor and Thrombosis Models. Arteriosclerosis, Thrombosis, and Vascular Biology. 2010;30(5):900-908. doi:10.1161/ATVBAHA.108.177477
12. Francischetti IMB, Seydel KB, Monteiro RQ. Blood Coagulation, Inflammation, and Malaria. Microcirculation. 2008;15(2):81-107. doi:10.1080/10739680701451516
13. Ruf W, Disse J, Carneiro-Lobo TC, Yokota N, Schaffner F. Tissue factor and cell signalling in cancer progression and thrombosis: TF in cancer. Journal of Thrombosis and Haemostasis. 2011;9:306-315. doi:10.1111/j.1538-7836.2011.04318.x
14. Coughlin SR. Protease-activated receptors in hemostasis, thrombosis and vascular biology. Journal of Thrombosis and Haemostasis. 2005;3(8):1800-1814. doi:10.1111/j.1538-7836.2005.01377.x
15. Versteeg H. Tissue Factor: Old and New Links with Cancer Biology. Seminars in Thrombosis and Hemostasis. 2015;41(07):747-755. doi:10.1055/s-0035-1556048
16. Gessler F, Voss V, Dützmann S, Seifert V, Gerlach R, Kögel D. Inhibition of tissue factor/protease-activated receptor-2 signaling limits proliferation, migration and invasion of malignant glioma cells. Neuroscience. 2010;165(4):1312-1322. doi:10.1016/j.neuroscience.2009.11.049
17. Carneiro-Lobo TC, Schaffner F, Disse J, et al. The tick-derived inhibitor Ixolaris prevents tissue factor signaling on tumor cells: Inhibitor Ixolaris prevents tissue factor signaling. Journal of Thrombosis and Haemostasis. 2012;10(9):1849-1858. doi:10.1111/j.1538-7836.2012.04864.x
18. Leppert U, Eisenreich A. The role of tissue factor isoforms in cancer biology: Role of TF isoforms in cancer biology. International Journal of Cancer. 2015;137(3):497-503. doi:10.1002/ijc.28959
19. Amarzguioui M. Ex vivo and In vivo Delivery of Anti-Tissue Factor Short Interfering RNA Inhibits Mouse Pulmonary Metastasis of B16 Melanoma Cells. Clinical Cancer Research. 2006;12(13):4055-4061. doi:10.1158/1078-0432.CCR-05-2482
20. Hisada Y, Mackman N. Tissue Factor and Extracellular Vesicles: Activation of Coagulation and Impact on Survival in Cancer. Cancers. 2021;13(15):3839. doi:10.3390/cancers13153839
21. Bromberg ME, Konigsberg WH, Madison JF, Pawashe A, Garen A. Tissue factor promotes melanoma metastasis by a pathway independent of blood coagulation. Proceedings of the National Academy of Sciences. 1995;92(18):8205-8209. doi:10.1073/pnas.92.18.8205
22. Amirkhosravi A, Meyer T, Chang JY, et al. Tissue Factor Pathway Inhibitor Reduces Experimental Lung Metastasis of B16 Melanoma. Thrombosis and Haemostasis. 2002;87(06):930-936. doi:10.1055/s-0037-1613114
23. Voigtländer C, Rand A, Liu SL, et al. Suppression of tissue factor expression, cofactor activity, and metastatic potential of murine melanoma cells by the N -terminal domain of adenovirus E1A 12S protein: Inhibition of Tissue Factor Function in Melanoma Cells by E1A. Journal of Cellular Biochemistry. 2002;85(1):54-71. doi:10.1002/jcb.10099
24. Wang X, Wang M, Amarzguioui M, Liu F, Fodstad Ø, Prydz H. Downregulation of tissue factor by RNA interference in human melanoma LOX-L cells reduces pulmonary metastasis in nude mice. International Journal of Cancer. 2004;112(6):994-1002. doi:10.1002/ijc.20527
25. Monteiro RQ. Targeting exosites on blood coagulation proteases. Anais da Academia Brasileira de Ciências. 2005;77(2):275-280.
26. Hembrough TA, Swartz GM, Papathanassiu A, et al. Tissue Factor/Factor VIIa Inhibitors Block Angiogenesis and Tumor Growth Through a Nonhemostatic Mechanism. :5.
27. Lee A, Agnelli G, Büller H, et al. Dose-Response Study of Recombinant Factor VIIa/Tissue Factor Inhibitor Recombinant Nematode Anticoagulant Protein c2 in Prevention of Postoperative Venous Thromboembolism in Patients Undergoing Total Knee Replacement. Circulation. 2001;104(1):74-78. doi:10.1161/hc2601.091386
28. Carneiro-Lobo TC, Konig S, Machado DE, et al. Ixolaris, a tissue factor inhibitor, blocks primary tumor growth and angiogenesis in a glioblastoma model. Journal of Thrombosis and Haemostasis. 2009;7(11):1855-1864. doi:10.1111/j.1538-7836.2009.03553.x
29. de Oliveira ADS, Lima LG, Mariano-Oliveira A, et al. Inhibition of tissue factor by ixolaris reduces primary tumor growth and experimental metastasis in a murine model of melanoma. Thrombosis Research. 2012;130(3):e163-e170. doi:10.1016/j.thromres.2012.05.021
30. Barboza T, Gomes T, Mizurini DM, et al. 99mTc-ixolaris targets glioblastoma-associated tissue factor: In vitro and pre-clinical applications. Thrombosis Research. 2015;136(2):432-439. doi:10.1016/j.thromres.2015.05.032
31. Barboza T, Gomes T, da Costa Medeiros P, et al. Development of 131I-ixolaris as a theranostic agent: metastatic melanoma preclinical studies. Clin Exp Metastasis. 2020;37(4):489-497. doi:10.1007/s10585-020-10036-0