Structure and function of von Willebrand factor

Hassan, Md. Imtaiyaz; Saxena, Aditya; Ahmad, Faizan

doi:10.1097/mbc.0b013e32834cb35d

Cited by 56 publications

(36 citation statements)

References 145 publications

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“…It functions as a mediator of platelet-endothelial/subendothelial adhesion to promote platelet aggregate formation, as well as a carrier for Factor VIII in the circulation [2–5]. In addition to its major role in hemostasis, VWF has been reported to participate in the immune response, inflammation, angiogenesis and cancer metastasis [6–8].…”

Section: Introductionmentioning

confidence: 99%

Functional assessment of von Willebrand factor expression by cancer cells of non-endothelial origin

et al. 2016

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Von Willebrand factor (VWF) is a highly adhesive procoagulant molecule that mediates platelet adhesion to endothelial and subendothelial surfaces. Normally it is expressed exclusively in endothelial cells (ECs) and megakaryocytes. However, a few studies have reported VWF detection in cancer cells of non-endothelial origin, including osteosarcoma. A role for VWF in cancer metastasis has long been postulated but evidence supporting both pro- and anti-metastatic roles for VWF has been presented. We hypothesized that the role of VWF in cancer metastasis is influenced by its cellular origin and that cancer cell acquisition of VWF expression may contribute to enhanced metastatic potential. We demonstrated de novo expression of VWF in glioma as well as osteosarcoma cells. Endothelial monolayer adhesion, transmigration and extravasation capacities of VWF expressing cancer cells were shown to be enhanced compared to non-VWF expressing cells, and were significantly reduced as a result of VWF knock down. VWF expressing cancer cells were also detected in patient tumor samples of varying histologies. Analyses of the mechanism of transcriptional activation of the VWF in cancer cells demonstrated a pattern of trans-activating factor binding and epigenetic modifications consistent overall with that observed in ECs. These results demonstrate that cancer cells of non-endothelial origin can acquire de novo expression of VWF, which can enhance processes, including endothelial and platelet adhesion and extravasation, that contribute to cancer metastasis.

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Section: Introductionmentioning

confidence: 99%

Functional assessment of von Willebrand factor expression by cancer cells of non-endothelial origin

et al. 2016

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“…After 4 weeks, immunohistochemistry was used to assess the density and size of vascular structures with the delivery of saline, composites without IL‐10, or composites with IL‐10 and representative images are shown in Figure 10 A–C. Von Willebrand factor (vWF) is a glycoprotein produced by endothelial cells and is present in the lumen of vascular structures of all sizes, from capillaries to arterioles, whereas alpha‐smooth muscle actin (α‐SMA) is expressed by smooth muscle cells and is only present in more mature vasculature . Both vWF + and vWF + α‐SMA + vascular structures contribute to enhancing perfusion in the border zone region after MI.…”

Section: Resultsmentioning

confidence: 99%

Injectable Supramolecular Hydrogel/Microgel Composites for Therapeutic Delivery

Chen

Chung

Mealy

et al. 2018

Macromolecular Bioscience

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Shear-thinning hydrogels are useful for biomedical applications, from 3D bioprinting to injectable biomaterials. Although they have the appropriate properties for injection, it may be advantageous to decouple injectability from the controlled release of encapsulated therapeutics. Toward this, composites of hydrogels and encapsulated microgels are introduced with microgels that are fabricated via microfluidics. The microgel crosslinker controls degradation and entrapped molecule release, and the concentration of microgels alters composite hydrogel rheological properties. For treatment of myocardial infarction (MI), interleukin-10 (IL-10) is encapsulated in microgels and released from composites. In a rat model of MI, composites with IL-10 reduce macrophage density after 1 week and improve scar thickness, ejection fraction, cardiac output, and the size of vascular structures after 4 weeks when compared to saline injection. Improvements are also observed with the composite without IL-10 over saline, emphasizing the role of injectable hydrogels alone on tissue repair.

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“…For example, Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organization, epithelial development, cell adhesion, protein folding, chromatin remodelling and zinc sensing [92]. We also found that NP_214882.1 and NP_215474.1 are showing similarity with von Willebrand factor with a type A domain, which is found to be responsible for various blood disorders [93][94][95]. Association of type A domain makes it liable to be involved in various significant activities such as cell adhesion and immune defense [96].…”

Section: Binding Proteinsmentioning

confidence: 94%