The Intriguing Connections between von Willebrand Factor, ADAMTS13 and Cancer

被引:17
作者
Colonne, Chanukya K. [1 ]
Favaloro, Emmanuel J. [1 ,2 ,3 ]
Pasalic, Leonardo [1 ,2 ,4 ]
机构
[1] Westmead Hosp, Inst Clin Pathol & Med Res ICPMR, Dept Haematol, NSW Hlth Pathol, Sydney, NSW 2145, Australia
[2] Sydney Ctr Thrombosis & Haemostasis, Sydney, NSW 2145, Australia
[3] Charles Sturt Univ, Fac Sci & Hlth, Wagga Wagga, NSW 2650, Australia
[4] Univ Sydney, Westmead Hosp, Westmead Clin Sch, Sydney, NSW 2145, Australia
关键词
cancer; von Willebrand factor; ADAMTS13; thrombosis; metastasis; thrombotic thrombocytopenic purpura; acquired von Willebrand disease; bleeding; biomarkers; THROMBOTIC THROMBOCYTOPENIC PURPURA; ACQUIRED VONWILLEBRAND DISEASE; PLATELET GLYCOPROTEIN-IB; ABO BLOOD-GROUP; HEPATOCELLULAR-CARCINOMA DEVELOPMENT; MOLECULAR-WEIGHT HEPARIN; FACTOR-CLEAVING PROTEASE; ESSENTIAL THROMBOCYTHEMIA; BREAST-CANCER; FACTOR-VIII;
D O I
10.3390/healthcare10030557
中图分类号
R19 [保健组织与事业(卫生事业管理)];
学科分类号
摘要
von Willebrand factor (VWF) is a complex and large protein that is cleaved by ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13), and together they serve important roles in normal hemostasis. Malignancy can result in both a deficiency or excess of VWF, leading to aberrant hemostasis with either increased bleeding or thrombotic complications, as respectively seen with acquired von Willebrand syndrome and cancer-associated venous thromboembolism. There is emerging evidence to suggest VWF also plays a role in inflammation, angiogenesis and tumor biology, and it is likely that VWF promotes tumor metastasis. High VWF levels have been documented in a number of malignancies and in some cases correlate with more advanced disease and poor prognosis. Tumor cells can induce endothelial cells to release VWF and certain tumor cells have the capacity for de novo expression of VWF, leading to a proinflammatory microenvironment that is likely conducive to tumor progression, metastasis and micro-thrombosis. VWF can facilitate tumor cell adhesion to endothelial cells and aids with the recruitment of platelets into the tumor microenvironment, where tumor/platelet aggregates are able to form and facilitate hematogenous spread of cancer. As ADAMTS13 moderates VWF level and activity, it too is potentially involved in the pathophysiology of these events. VWF and ADAMTS13 have been explored as tumor biomarkers for the detection and prognostication of certain malignancies; however, the results are underdeveloped and so currently not utilized for clinical use. Further studies addressing the basic science mechanisms and real word epidemiology are required to better appreciate the intriguing connections between VWF, ADAMTS13 and malignancy. A better understanding of the role VWF and ADAMTS13 play in the promotion and inhibition of cancer and its metastasis will help direct further translational studies to aid with the development of novel cancer prognostic tools and treatment modalities.
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页数:18
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