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Cell Spheroids with Enhanced Aggressiveness to Mimic Human Liver Cancer In Vitro and In Vivo

We fabricated a spheroid-forming unit (SFU) for efficient and economic production of cell spheroids. We optimized the protocol for generating large and homogenous liver cancer cell spheroids using Huh7 hepatocellular carcinoma (HCC) cells. The large Huh7 spheroids showed apoptotic and proliferative...

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Autores principales: Jung, Hong-Ryul, Kang, Hyun Mi, Ryu, Jea-Woon, Kim, Dae-Soo, Noh, Kyung Hee, Kim, Eun-Su, Lee, Ho-Joon, Chung, Kyung-Sook, Cho, Hyun-Soo, Kim, Nam-Soon, Im, Dong-Soo, Lim, Jung Hwa, Jung, Cho-Rok
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5585316/
https://www.ncbi.nlm.nih.gov/pubmed/28874716
http://dx.doi.org/10.1038/s41598-017-10828-7
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author Jung, Hong-Ryul
Kang, Hyun Mi
Ryu, Jea-Woon
Kim, Dae-Soo
Noh, Kyung Hee
Kim, Eun-Su
Lee, Ho-Joon
Chung, Kyung-Sook
Cho, Hyun-Soo
Kim, Nam-Soon
Im, Dong-Soo
Lim, Jung Hwa
Jung, Cho-Rok
author_facet Jung, Hong-Ryul
Kang, Hyun Mi
Ryu, Jea-Woon
Kim, Dae-Soo
Noh, Kyung Hee
Kim, Eun-Su
Lee, Ho-Joon
Chung, Kyung-Sook
Cho, Hyun-Soo
Kim, Nam-Soon
Im, Dong-Soo
Lim, Jung Hwa
Jung, Cho-Rok
author_sort Jung, Hong-Ryul
collection PubMed
description We fabricated a spheroid-forming unit (SFU) for efficient and economic production of cell spheroids. We optimized the protocol for generating large and homogenous liver cancer cell spheroids using Huh7 hepatocellular carcinoma (HCC) cells. The large Huh7 spheroids showed apoptotic and proliferative signals in the centre and at the surface, respectively. In particular, hypoxia-induced factor-1 alpha (HIF-1α) and ERK signal activation were detected in the cell spheroids. To diminish core necrosis and increase the oncogenic character, we co-cultured spheroids with 2% human umbilical vein endothelial cells (HUVECs). HUVECs promoted proliferation and gene expression of HCC-related genes and cancer stem cell markers in the Huh7 spheroidsby activating cytokine signalling, mimicking gene expression in liver cancer. HUVECs induced angiogenesis and vessel maturation in Huh7 spheroids in vivo by activating epithelial–mesenchymal transition and angiogenic pathways. The large Huh7 cell spheroids containing HUVECs survived at higher concentrations of anti-cancer drugs (doxorubicin and sorafenib) than did monolayer cells. Our large cell spheroid provides a useful in vitro HCC model to enable intuitive observation for anti-cancer drug testing.
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spelling pubmed-55853162017-09-06 Cell Spheroids with Enhanced Aggressiveness to Mimic Human Liver Cancer In Vitro and In Vivo Jung, Hong-Ryul Kang, Hyun Mi Ryu, Jea-Woon Kim, Dae-Soo Noh, Kyung Hee Kim, Eun-Su Lee, Ho-Joon Chung, Kyung-Sook Cho, Hyun-Soo Kim, Nam-Soon Im, Dong-Soo Lim, Jung Hwa Jung, Cho-Rok Sci Rep Article We fabricated a spheroid-forming unit (SFU) for efficient and economic production of cell spheroids. We optimized the protocol for generating large and homogenous liver cancer cell spheroids using Huh7 hepatocellular carcinoma (HCC) cells. The large Huh7 spheroids showed apoptotic and proliferative signals in the centre and at the surface, respectively. In particular, hypoxia-induced factor-1 alpha (HIF-1α) and ERK signal activation were detected in the cell spheroids. To diminish core necrosis and increase the oncogenic character, we co-cultured spheroids with 2% human umbilical vein endothelial cells (HUVECs). HUVECs promoted proliferation and gene expression of HCC-related genes and cancer stem cell markers in the Huh7 spheroidsby activating cytokine signalling, mimicking gene expression in liver cancer. HUVECs induced angiogenesis and vessel maturation in Huh7 spheroids in vivo by activating epithelial–mesenchymal transition and angiogenic pathways. The large Huh7 cell spheroids containing HUVECs survived at higher concentrations of anti-cancer drugs (doxorubicin and sorafenib) than did monolayer cells. Our large cell spheroid provides a useful in vitro HCC model to enable intuitive observation for anti-cancer drug testing. Nature Publishing Group UK 2017-09-05 /pmc/articles/PMC5585316/ /pubmed/28874716 http://dx.doi.org/10.1038/s41598-017-10828-7 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Jung, Hong-Ryul
Kang, Hyun Mi
Ryu, Jea-Woon
Kim, Dae-Soo
Noh, Kyung Hee
Kim, Eun-Su
Lee, Ho-Joon
Chung, Kyung-Sook
Cho, Hyun-Soo
Kim, Nam-Soon
Im, Dong-Soo
Lim, Jung Hwa
Jung, Cho-Rok
Cell Spheroids with Enhanced Aggressiveness to Mimic Human Liver Cancer In Vitro and In Vivo
title Cell Spheroids with Enhanced Aggressiveness to Mimic Human Liver Cancer In Vitro and In Vivo
title_full Cell Spheroids with Enhanced Aggressiveness to Mimic Human Liver Cancer In Vitro and In Vivo
title_fullStr Cell Spheroids with Enhanced Aggressiveness to Mimic Human Liver Cancer In Vitro and In Vivo
title_full_unstemmed Cell Spheroids with Enhanced Aggressiveness to Mimic Human Liver Cancer In Vitro and In Vivo
title_short Cell Spheroids with Enhanced Aggressiveness to Mimic Human Liver Cancer In Vitro and In Vivo
title_sort cell spheroids with enhanced aggressiveness to mimic human liver cancer in vitro and in vivo
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5585316/
https://www.ncbi.nlm.nih.gov/pubmed/28874716
http://dx.doi.org/10.1038/s41598-017-10828-7
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