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

Abstract

Endothelial cells (ECs), as a tumor niche cell, generate and secrete Von Willebrand factor (VWF) that is linked to osteosarcoma (OS) progression. However, the role and regulatory mechanisms of VWF that underpin OS progression remain unclear. Here, using a coculture system ex vivo, we showed that ECs promoted the epithelial-mesenchymal transition (EMT) process in OS cells via enhanced VWF secretion. VWF secreted by ECs directly contributed to OS EMT and metastasis by activating NF-κB signaling. In addition, OS cells exerted a feedback effect on ECs to promote VWF release via activation of phospholipase D 1 signaling, through which enhanced VWF secretion results in further tumor deterioration. To conclude, ECs served as a modulator and an effector of OS, accelerating OS exacerbation by VWF release.

• Authors: Jing Ling, Yu Sun, Jun Pan, Huan Wang, Zhenni Ma, Jie Yin, Zhaohua Bao, Huilin Yang, Ling Liu
• Journal: Journal of cellular biochemistry (J Cell Biochem) Vol. 120 Issue 9 Pg. 15971-15979 (09 2019) ISSN: 1097-4644 [Electronic] United States
• PMID: 31099074 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 Wiley Periodicals, Inc.

Chemical References

• NF-kappa B
• von Willebrand Factor
• Phospholipase D
• phospholipase D1

Topics

• Animals
• Bone Neoplasms (genetics, metabolism, pathology)
• Cell Line, Tumor
• Coculture Techniques
• Disease Progression
• Endothelial Cells (cytology, metabolism)
• Epithelial-Mesenchymal Transition
• Feedback, Physiological
• Human Umbilical Vein Endothelial Cells
• Humans
• Mice
• NF-kappa B (metabolism)
• Neoplasm Metastasis
• Neoplasm Transplantation
• Osteosarcoma (genetics, metabolism, pathology)
• Phospholipase D (metabolism)
• Signal Transduction
• von Willebrand Factor (metabolism)