Physical supports from liver cancer cells are essential for differentiation and remodeling of endothelial cells in a HepG2-HUVEC co-culture model

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 fro...

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Main Authors: Low, Kar Perng, Chiew, Geraldine Giap Ying, Fu, Afu, Luo, Kathy Qian
Other Authors: School of Chemical and Biomedical Engineering
Format: Article
Language:English
Published: 2015
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Online Access:https://hdl.handle.net/10356/106040
http://hdl.handle.net/10220/26276
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-1060402023-12-29T06:52:14Z Physical supports from liver cancer cells are essential for differentiation and remodeling of endothelial cells in a HepG2-HUVEC co-culture model Low, Kar Perng Chiew, Geraldine Giap Ying Fu, Afu Luo, Kathy Qian School of Chemical and Biomedical Engineering DRNTU::Science::Biological sciences::Microbiology 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. Published version 2015-07-06T06:10:47Z 2019-12-06T22:03:28Z 2015-07-06T06:10:47Z 2019-12-06T22:03:28Z 2015 2015 Journal Article 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-. 2045-2322 https://hdl.handle.net/10356/106040 http://hdl.handle.net/10220/26276 10.1038/srep10801 26053957 en Scientific reports 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 http://creativecommons.org/licenses/by/4.0/ 16 p. application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic DRNTU::Science::Biological sciences::Microbiology
spellingShingle DRNTU::Science::Biological sciences::Microbiology
Low, Kar Perng
Chiew, Geraldine Giap Ying
Fu, Afu
Luo, Kathy Qian
Physical supports from liver cancer cells are essential for differentiation and remodeling of endothelial cells in a HepG2-HUVEC co-culture model
description 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.
author2 School of Chemical and Biomedical Engineering
author_facet School of Chemical and Biomedical Engineering
Low, Kar Perng
Chiew, Geraldine Giap Ying
Fu, Afu
Luo, Kathy Qian
format Article
author Low, Kar Perng
Chiew, Geraldine Giap Ying
Fu, Afu
Luo, Kathy Qian
author_sort Low, Kar Perng
title Physical supports from liver cancer cells are essential for differentiation and remodeling of endothelial cells in a HepG2-HUVEC co-culture model
title_short Physical supports from liver cancer cells are essential for differentiation and remodeling of endothelial cells in a HepG2-HUVEC co-culture model
title_full Physical supports from liver cancer cells are essential for differentiation and remodeling of endothelial cells in a HepG2-HUVEC co-culture model
title_fullStr Physical supports from liver cancer cells are essential for differentiation and remodeling of endothelial cells in a HepG2-HUVEC co-culture model
title_full_unstemmed Physical supports from liver cancer cells are essential for differentiation and remodeling of endothelial cells in a HepG2-HUVEC co-culture model
title_sort physical supports from liver cancer cells are essential for differentiation and remodeling of endothelial cells in a hepg2-huvec co-culture model
publishDate 2015
url https://hdl.handle.net/10356/106040
http://hdl.handle.net/10220/26276
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