The role of von Willebrand factor in breast cancer metastasis

Goh, Chia Yin; Patmore, Sean; Smolenski, Albert; Howard, Jane; Evans, Shane; O’Sullivan, Jamie M.; McCann, Amanda

doi:10.1016/j.tranon.2021.101033

Cited by 21 publications

(10 citation statements)

References 89 publications

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“…Overall, only a limited number of recurrent somatic mutations were detected in our pediatric RCC samples, most notably CCDC168, LRRK2 , PLEKHA1 , VWF , and MAP3K9 , with the majority of them being reported in RCC in general for the first time. Interestingly, LRRK2 , VWF , and various MAPK genes (i.e., MAP4K3 , MAP4K1 ) mutated in metastatic MiT-pRCC cases have been reported as potential drug targets, mostly in pre-clinical models ( Goh et al., 2021 ; Johnson et al., 2019 ; Mancini et al., 2020 ). Furthermore, analysis of differentially expressed genes revealed a limited number of potential drug targets unreported so far for MiT-pRCC such as NTSR2, CYP17A1, CHRM4, CA3, and PTGER3, besides VEGFA/HIF1A and RET with a lower degree of overexpression.…”

Section: Discussionmentioning

confidence: 99%

The genomic landscape of pediatric renal cell carcinomas

et al. 2022

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Section: Discussionmentioning

confidence: 99%

The genomic landscape of pediatric renal cell carcinomas

et al. 2022

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“…At a paradox to the evidence supporting a pro-metastatic role for VWF, there is evidence to suggest that VWF also plays a role in inhibiting tumor angiogenesis and promoting apoptosis [ 73 , 125 ]. VWF knockout mice have increased the pulmonary metastatic burden in mouse models of metastatic Lewis-lung carcinoma and melanoma [ 126 ].…”

Section: Vwf Adamts13 and Cancer Metastasis Riskmentioning

confidence: 99%

“…A specific HDAC inhibitor, MS-275, has been shown to significantly reduce tumor growth, decrease VWF-positive blood vessels, decrease lung metastasis and reverse epithelial-mesenchymal transition in an in vivo murine model of breast cancer [ 162 ]. Given the relationship between HDAC and VWF gene expression, and the previously discussed mechanisms by which the VWF may promote tumor metastasis, it is possible that the effect of HDAC inhibitors in attenuating breast cancer metastasis may include the targeting of VWF expression [ 125 ].…”

Section: Vwf As a Potential Target For Cancer Therapymentioning

confidence: 99%

The Intriguing Connections between von Willebrand Factor, ADAMTS13 and Cancer

2022

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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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“…Moreover, CSC-initiated angiogenesis via factors like VEGF, Ang-2, MIP-2, TGF-β1, IL-6, and IL-8 as well as vasculogenic mimicry are also regulated by stemness pathways [111,[117][118][119]. Angiogenetic factors like the von Willebrand factor [120][121][122][123], Tspan-8 [124,125], the chemokines CXCL5 [126][127][128][129] and MIF [130][131][132][133], the CCR chemokine receptor family [50,[134][135][136] are often mediated through exosomes to ensure vascular up flux and endothelial regeneration [111][112][113]137]. The ECM, a core element of the TME, also plays a critical role in determining proliferative tendencies during angiogenesis as well as regulating CSC differentiative capacity by impacting cellular stiffness [4,5,114,138].…”

Section: Stem Cell Involvement In Tumor Microenvironment Regulationmentioning

confidence: 99%

Cancer Stem Cells and the Tumor Microenvironment: Targeting the Critical Crosstalk through Nanocarrier Systems

Nayak

Warrier

Kumar

2022

Stem Cell Rev and Rep

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The physiological state of the tumor microenvironment (TME) plays a central role in cancer development due to multiple universal features that transcend heterogeneity and niche specifications, like promoting cancer progression and metastasis. As a result of their preponderant involvement in tumor growth and maintenance through several microsystemic alterations, including hypoxia, oxidative stress, and acidosis, TMEs make for ideal targets in both diagnostic and therapeutic ventures. Correspondingly, methodologies to target TMEs have been investigated this past decade as stratagems of significant potential in the genre of focused cancer treatment. Within targeted oncotherapy, nanomedical derivates—nanocarriers (NCs) especially—have emerged to present notable prospects in enhancing targeting specificity. Yet, one major issue in the application of NCs in microenvironmental directed therapy is that TMEs are too broad a spectrum of targeting possibilities for these carriers to be effectively employed. However, cancer stem cells (CSCs) might portend a solution to the above conundrum: aside from being quite heavily invested in tumorigenesis and therapeutic resistance, CSCs also show self-renewal and fluid clonogenic properties that often define specific TME niches. Further scrutiny of the relationship between CSCs and TMEs also points towards mechanisms that underly tumoral characteristics of metastasis, malignancy, and even resistance. This review summarizes recent advances in NC-enabled targeting of CSCs for more holistic strikes against TMEs and discusses both the current challenges that hinder the clinical application of these strategies as well as the avenues that can further CSC-targeting initiatives. Graphical abstract Central role of CSCs in regulation of cellular components within the TME

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The role of von Willebrand factor in breast cancer metastasis

Cited by 21 publications

References 89 publications

The genomic landscape of pediatric renal cell carcinomas

The genomic landscape of pediatric renal cell carcinomas

The Intriguing Connections between von Willebrand Factor, ADAMTS13 and Cancer

Cancer Stem Cells and the Tumor Microenvironment: Targeting the Critical Crosstalk through Nanocarrier Systems

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