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Title: Physical supports from liver cancer cells are essential for differentiation and remodeling of endothelial cells in a HepG2-HUVEC co-culture model
Authors: Low, Kar Perng
Chiew, Geraldine Giap Ying
Fu, Afu
Luo, Kathy Qian
Keywords: DRNTU::Science::Biological sciences::Microbiology
Issue Date: 2015
Source: Chiew, G. G. Y., Fu, A., Low, K. P., & Luo, K. Q. (2015). Physical supports from liver cancer cells are essential for differentiation and remodeling of endothelial cells in a HepG2-HUVEC co-culture model. Scientific reports, 5, 10801-.
Series/Report no.: Scientific reports
Abstract: Blood vessel remodeling is crucial in tumor growth. Growth factors released by tumor cells and endothelium-extracellular matrix interactions are highlighted in tumor angiogenesis, however the physical tumor-endothelium interactions are highly neglected. Here, we report that the physical supports from hepatocellular carcinoma, HepG2 cells, are essential for the differentiation and remodeling of endothelial cells. In a HepG2-HUVEC co-culture model, endothelial cells in direct contact with HepG2 cells could differentiate and form tubular structures similar to those plated on matrigel. By employing HepG2 cell sheet as a supportive layer, endothelial cells formed protrusions and sprouts above it. In separate experiments, fixed HepG2 cells could stimulate endothelial cells differentiation while the conditioned media could not, indicating that physical interactions between tumor and endothelial cells were indispensable. To further investigate the endothelium-remodeling mechanisms, the co-culture model was treated with inhibitors targeting different angiogenic signaling pathways. Inhibitors targeting focal adhesions effectively inhibited the differentiation of endothelial cells, while the growth factor receptor inhibitor displayed little effect. In conclusion, the co-culture model has provided evidences of the essential role of cancer cells in the differentiation and remodeling of endothelial cells, and is a potential platform for the discovery of new anti-angiogenic agents for liver cancer therapy.
ISSN: 2045-2322
DOI: 10.1038/srep10801
Rights: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit
Fulltext Permission: open
Fulltext Availability: With Fulltext
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