von Willebrand factor expression in osteosarcoma metastasis

Eppert, Kolja; Wunder, Jay S.; Aneliunas, Vicky; Kandel, Rita A.; Andrulis, Irene L.

doi:10.1038/modpathol.3800265

Cited by 48 publications

(49 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, there have been a few reports of VWF detection in cancer cells of non-endothelial origin. VWF protein was reported in cultured human osteosarcoma SAOS2 cells, human colorectal SW480 cancer cells, and recently in two hepatocellular carcinoma cell lines HepG2 and BEL7402 [20–22]. In these studies, increased levels of VWF in osteosarcoma and hepatocellular carcinoma tumor tissues in situ were demonstrated and associated with increased metastasis and clinicopathologic staging [20, 21].…”

Section: Introductionmentioning

confidence: 99%

“…VWF protein was reported in cultured human osteosarcoma SAOS2 cells, human colorectal SW480 cancer cells, and recently in two hepatocellular carcinoma cell lines HepG2 and BEL7402 [20–22]. In these studies, increased levels of VWF in osteosarcoma and hepatocellular carcinoma tumor tissues in situ were demonstrated and associated with increased metastasis and clinicopathologic staging [20, 21]. Increased VWF levels were not associated with increased vascular density [20], suggesting that increased VWF expression may have a cellular origin that is distinct from vascular ECs.…”

Section: Introductionmentioning

confidence: 99%

“…In these studies, increased levels of VWF in osteosarcoma and hepatocellular carcinoma tumor tissues in situ were demonstrated and associated with increased metastasis and clinicopathologic staging [20, 21]. Increased VWF levels were not associated with increased vascular density [20], suggesting that increased VWF expression may have a cellular origin that is distinct from vascular ECs. Based on these reports, we explored whether some cancer cells of non-endothelial origin, including glioma as well as osteosarcoma SAOS2, acquire de novo transcription of the VWF gene and determined the functional consequences with regard to tumor cell adhesion and extravasation.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

et al. 2016

View full text Add to dashboard Cite

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.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2016

View full text Add to dashboard Cite

show abstract

“…In an attempt to assess the angiogenic potential of CLS formed on the various ECM, we analyzed CLS for vWF, a large glycoprotein that not only participates in vascular hemostasis via binding of platelets to the subendothelial matrix but has been associated with tumor metastasis (22,76). One important means whereby tumor cells metastasize is via their adhesion to the capillary wall prior to extravasation, a process mediated by platelet aggregation to tumor cells (54,56).…”

Section: Discussionmentioning

confidence: 99%

Breast cancer cell-derived matrix supports vascular morphogenesis

Hielscher

Qiu

Gerecht

2012

American Journal of Physiology-Cell Physiology

View full text Add to dashboard Cite

The extracellular matrix (ECM), important for maintaining tissue homeostasis, is abnormally expressed in mammary tumors and additionally plays a crucial role in angiogenesis. We hypothesize that breast cancer cells (BCCs) deposit ECM that supports unique patterns of vascular morphogenesis of endothelial cells (ECs). Evaluation of ECM expression revealed that a nontumorigenic cell line (MCF10A), a tumorigenic cell line (MCF7), and a metastatic cell line (MDA-MB-231) express collagens I and IV, fibronectin, and laminin, with tenascin-C limited to MCF10A and MCF7. The amount of ECM deposited by BCCs was found to be higher in MCF10A compared with MCF7 and MDA231, with all ECM differing in their gross structure but similar in mean fiber diameter. Nonetheless, deposition of ECM from BCC lines was overall difficult to detect and insufficient to support capillary-like structure (CLS) formation of ECs. Therefore, a coculture approach was undertaken in which individual BCC lines were cocultured with fibroblasts. Variation in abundance of deposited ECM, deposition of ECM proteins, such as absent collagen I deposition from MDA231-fibroblast cocultures, and fibril organization was found. Deposited ECM from fibroblasts and each coculture supported rapid CLS formation of ECs. Evaluation of capillary properties revealed that CLS grown on ECM deposited from MDA231-fibroblast cocultures possessed significantly larger lumen diameters, occupied the greatest percentage of area, expressed the highest levels of von Willebrand factor, and expressed the greatest amount of E-selectin, which was upregulated independent of exposure to TNF-α. To our knowledge, this is the first study to report tumor cell ECM-mediated differences in vascular capillary features, and thus offers the framework for future investigations interrogating the role of the tumor ECM in supporting vascular morphogenesis.

show abstract

“…It has become one of the most common primary malignant bone tumors in childhood and adult (Eppert et al, 2005;Tan et al, 2009). Clearly, the impact of identifying factors that govern proliferation and progression is useful in the management of osteosarcoma.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-802 Promotes Osteosarcoma Cell Proliferation by Targeting p27

Cao¹,

Shen²,

Huang³

2013

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

MicroRNAs have been demonstrated to regulate proliferation and apoptosis in many types of cancers, but biological functions in osteosarcomas remain relatively unknown. Here, we found expression of miR-802 to be up-regulated in osteosarcoma tissues in comparison with adjacent normal tissues. Enforced expression of miR-802 was able to promote cell proliferation in U2OS and MG63 cells, while miR-802 antisense oligonucleotides (antisense miR-802) inhibited cell proliferation. At the molecular level, our results further revealed that expression of p27, a negative cell-cycle regulator, was negatively regulated by miR-802. Therefore, the data reported here indicate that miR-802 is an important regulator in osteosarcoma, our findings contributing to a better understanding of important mis-regulated miRNAs in this tumour type.

show abstract

von Willebrand factor expression in osteosarcoma metastasis

Cited by 48 publications

References 46 publications

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

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

Breast cancer cell-derived matrix supports vascular morphogenesis

MicroRNA-802 Promotes Osteosarcoma Cell Proliferation by Targeting p27

Contact Info

Product

Resources

About