Feedback modulation of endothelial cells promotes epithelial‐mesenchymal transition and metastasis of osteosarcoma cells by Von Willebrand Factor release

Ling, Jing; Sun, Yu; Wang, Huan; Ma, Zhengliang; Yin, Jing; Bao, Zhaohua; Yang, Huilin; Liu, Ling

doi:10.1002/jcb.28875

Cited by 11 publications

(7 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recent studies by Liu et al confirmed that EMT activation can increase the invasion and metastasis ability of osteosarcoma cells, and promote the progression of osteosarcoma [27,28]. The main features of EMT activation include down-regulation of epithelial cell markers such as E-cadherin, and increased expression of mesenchymal phenotypic markers such as Vimentin and N-cadherin [29,30]. Our study found that after PRR11 was downregulated, the invasion and migration ability of osteosarcoma cells U2OS was significantly reduced.…”

Section: Discussionsupporting

confidence: 68%

Down-regulation of PRR11 affects the proliferation, migration and invasion of osteosarcoma by inhibiting the Wnt/β-catenin pathway

Li¹,

Yu²,

Zhao³

et al. 2021

J. Cancer

View full text Add to dashboard Cite

This study aim to explore the effect of down-regulation of PRR11 (proline-rich protein 11) on the proliferation, invasion, migration, Wnt/β-catenin signaling pathway and EMT of osteosarcoma cells. Methods: Immunohistochemical staining, fluorescent quantitative PCR and western blotting were used to detect the expression level of PRR11 in osteosarcoma tissues and osteosarcoma cells. After SiRNA down-regulated the expression level of PRR11, CCK8 was used to detect cell proliferation ability, Transwell chamber to detect cell invasion ability, scratch test to detect cell migration ability, and flow cytometry to detect cell apoptosis. Western blotting was used to detect the expression levels of wnt/β-catenin pathway related proteins and key epithelial-mesenchymal transition proteins. Results: PRR11 is highly expressed in osteosarcoma tissues, and its expression level is related to tumor size, Enneking stage of tumor, lymph node metastasis and patient prognosis. The low expression of PRR11 can inhibit the proliferation, migration and invasion of osteosarcoma cells, and promote apoptosis. Down-regulating the expression of PRR11 will inhibit the expression of Wnt pathway related proteins β-catenin and p-GSK-3β, enhance the expression of p-β-catenin, GSK-3β, and increase the expression of downstream genes CyclinD1 and c-Myc in the Wnt pathway. At the same time, the expression of PRR11 was down-regulated, the epithelial marker E-cadherin was significantly increased, and the expression levels of mesenchymal markers Vimentin and Fibronectin were significantly reduced. Conclusion: Down-regulation of PRR11 can inhibit the proliferation, migration and invasion of osteosarcoma cells, and its mechanism may be related to down-regulation of PRR11 to inhibit the Wnt/β-catenin signaling pathway and thus prevent the EMT process. Therefore, PRR11 may be used as an oncogene to promote the occurrence and development of osteosarcoma, and is a potential prognostic indicator and therapeutic target in osteosarcoma.

show abstract

Section: Discussionsupporting

confidence: 68%

Down-regulation of PRR11 affects the proliferation, migration and invasion of osteosarcoma by inhibiting the Wnt/β-catenin pathway

Li¹,

Yu²,

Zhao³

et al. 2021

J. Cancer

View full text Add to dashboard Cite

show abstract

“…VWF may also promote the transformation of tumor cells to facilitate metastasis as well. For instance, VWF released by endothelial cells, when co-cultured with osteosarcoma cells, induces the osteosarcoma cells to undergo epithelial mesenchymal transitioning, which is an essential step in tumor metastasis [ 118 ].…”

Section: Vwf Adamts13 and Cancer Metastasis Riskmentioning

confidence: 99%

The Intriguing Connections between von Willebrand Factor, ADAMTS13 and Cancer

2022

View full text Add to dashboard Cite

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.

show abstract

“…Cancer cells promote the secretion of WPBs and vWF from ECs (237,238) and elevated plasmatic vWF correlate with tumor grade and metastasis (239). Moreover, vWF secretion has been reported to contribute to the process of EMT (240), the secretion of pro-inflammatory cytokines, and vascular permeability (234). Several studies show vWFdependent cancer cell adhesion to the endothelium is mediated by integrin receptors and facilitates extravasation during metastasis (239,(241)(242)(243).…”

Section: Coagulation Cascade and Autophagy In The Tumor Endotheliummentioning

confidence: 99%

Deciphering the Role of the Coagulation Cascade and Autophagy in Cancer-Related Thrombosis and Metastasis

et al. 2020

View full text Add to dashboard Cite

Thrombotic complications are the second leading cause of death among oncology patients worldwide. Enhanced thrombogenesis has multiple origins and may result from a deregulation of megakaryocyte platelet production in the bone marrow, the synthesis of coagulation factors in the liver, and coagulation factor signaling upon cancer and the tumor microenvironment (TME). While a hypercoagulable state has been attributed to factors such as thrombocytosis, enhanced platelet aggregation and Tissue Factor (TF) expression on cancer cells, further reports have suggested that coagulation factors can enhance metastasis through increased endothelial-cancer cell adhesion and enhanced endothelial cell activation. Autophagy is highly associated with cancer survival as a double-edged sword, as can both inhibit and promote cancer progression. In this review, we shall dissect the crosstalk between the coagulation cascade and autophagic pathway and its possible role in metastasis and cancer-associated thrombosis formation. The signaling of the coagulation cascade through the autophagic pathway within the hematopoietic stem cells, the endothelial cell and the cancer cell are discussed. Relevant to the coagulation cascade, we also examine the role of autophagy-related pathways in cancer treatment. In this review, we aim to bring to light possible new areas of cancer investigation and elucidate strategies for future therapeutic intervention.

show abstract

Feedback modulation of endothelial cells promotes epithelial‐mesenchymal transition and metastasis of osteosarcoma cells by Von Willebrand Factor release

Cited by 11 publications

References 32 publications

Down-regulation of PRR11 affects the proliferation, migration and invasion of osteosarcoma by inhibiting the Wnt/β-catenin pathway

Down-regulation of PRR11 affects the proliferation, migration and invasion of osteosarcoma by inhibiting the Wnt/β-catenin pathway

The Intriguing Connections between von Willebrand Factor, ADAMTS13 and Cancer

Deciphering the Role of the Coagulation Cascade and Autophagy in Cancer-Related Thrombosis and Metastasis

Contact Info

Product

Resources

About