Highly tumorigenic hepatocellular carcinoma cell line with cancer stem cell-like properties.
There are limited numbers of models to study hepatocellular carcinoma (HCC) in vivo in immunocompetent hosts. In an effort to develop a cell line with improved tumorigenicity, we derived a new cell line from Hepa1-6 cells through an in vivo passage in C57BL/6 mice. The resulting Dt81Hepa1-6 cell lin...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2017-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5289561?pdf=render |
| _version_ | 1818922779148288000 |
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| author | Benoit Lacoste Valérie-Ann Raymond Shamir Cassim Pascal Lapierre Marc Bilodeau |
| author_facet | Benoit Lacoste Valérie-Ann Raymond Shamir Cassim Pascal Lapierre Marc Bilodeau |
| author_sort | Benoit Lacoste |
| collection | DOAJ |
| description | There are limited numbers of models to study hepatocellular carcinoma (HCC) in vivo in immunocompetent hosts. In an effort to develop a cell line with improved tumorigenicity, we derived a new cell line from Hepa1-6 cells through an in vivo passage in C57BL/6 mice. The resulting Dt81Hepa1-6 cell line showed enhanced tumorigenicity compared to Hepa1-6 with more frequent (28±12 vs. 0±0 lesions at 21 days) and more rapid tumor development (21 (100%) vs. 70 days (10%)) in C57BL/6 mice. The minimal Dt81Hepa1-6 cell number required to obtain visible tumors was 100,000 cells. The Dt81Hepa1-6 cell line showed high hepatotropism with subcutaneous injection leading to liver tumors without development of tumors in lungs or spleen. In vitro, Dt81Hepa1-6 cells showed increased anchorage-independent growth (34.7±6.8 vs. 12.3±3.3 colonies; P<0.05) and increased EpCAM (8.7±1.1 folds; P<0.01) and β-catenin (5.4±1.0 folds; P<0.01) expression. A significant proportion of Dt81Hepa1-6 cells expressed EpCAM compared to Hepa1-6 (34.8±1.1% vs 0.9±0.13%; P<0.001). Enriched EpCAM+ Dt81Hepa1-6 cells led to higher tumor load than EpCAM- Dt81Hepa1-6 cells (1093±74 vs 473±100 tumors; P<0.01). The in vivo selected Dt81Hepa1-6 cell line shows high liver specificity and increased tumorigenicity compared to Hepa1-6 cells. These properties are associated with increased expression of EpCAM and β-catenin confirming that EpCAM+ HCC cells comprise a subset with characteristics of tumor-initiating cells with stem/progenitor cell features. The Dt81Hepa1-6 cell line with its cancer stem cell-like properties will be a useful tool for the study of hepatocellular carcinoma in vivo. |
| first_indexed | 2024-12-20T01:58:57Z |
| format | Article |
| id | doaj.art-daada33d65d84f8e8ef35f353c3155ed |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-20T01:58:57Z |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-daada33d65d84f8e8ef35f353c3155ed2022-12-21T19:57:24ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01122e017121510.1371/journal.pone.0171215Highly tumorigenic hepatocellular carcinoma cell line with cancer stem cell-like properties.Benoit LacosteValérie-Ann RaymondShamir CassimPascal LapierreMarc BilodeauThere are limited numbers of models to study hepatocellular carcinoma (HCC) in vivo in immunocompetent hosts. In an effort to develop a cell line with improved tumorigenicity, we derived a new cell line from Hepa1-6 cells through an in vivo passage in C57BL/6 mice. The resulting Dt81Hepa1-6 cell line showed enhanced tumorigenicity compared to Hepa1-6 with more frequent (28±12 vs. 0±0 lesions at 21 days) and more rapid tumor development (21 (100%) vs. 70 days (10%)) in C57BL/6 mice. The minimal Dt81Hepa1-6 cell number required to obtain visible tumors was 100,000 cells. The Dt81Hepa1-6 cell line showed high hepatotropism with subcutaneous injection leading to liver tumors without development of tumors in lungs or spleen. In vitro, Dt81Hepa1-6 cells showed increased anchorage-independent growth (34.7±6.8 vs. 12.3±3.3 colonies; P<0.05) and increased EpCAM (8.7±1.1 folds; P<0.01) and β-catenin (5.4±1.0 folds; P<0.01) expression. A significant proportion of Dt81Hepa1-6 cells expressed EpCAM compared to Hepa1-6 (34.8±1.1% vs 0.9±0.13%; P<0.001). Enriched EpCAM+ Dt81Hepa1-6 cells led to higher tumor load than EpCAM- Dt81Hepa1-6 cells (1093±74 vs 473±100 tumors; P<0.01). The in vivo selected Dt81Hepa1-6 cell line shows high liver specificity and increased tumorigenicity compared to Hepa1-6 cells. These properties are associated with increased expression of EpCAM and β-catenin confirming that EpCAM+ HCC cells comprise a subset with characteristics of tumor-initiating cells with stem/progenitor cell features. The Dt81Hepa1-6 cell line with its cancer stem cell-like properties will be a useful tool for the study of hepatocellular carcinoma in vivo.http://europepmc.org/articles/PMC5289561?pdf=render |
| spellingShingle | Benoit Lacoste Valérie-Ann Raymond Shamir Cassim Pascal Lapierre Marc Bilodeau Highly tumorigenic hepatocellular carcinoma cell line with cancer stem cell-like properties. PLoS ONE |
| title | Highly tumorigenic hepatocellular carcinoma cell line with cancer stem cell-like properties. |
| title_full | Highly tumorigenic hepatocellular carcinoma cell line with cancer stem cell-like properties. |
| title_fullStr | Highly tumorigenic hepatocellular carcinoma cell line with cancer stem cell-like properties. |
| title_full_unstemmed | Highly tumorigenic hepatocellular carcinoma cell line with cancer stem cell-like properties. |
| title_short | Highly tumorigenic hepatocellular carcinoma cell line with cancer stem cell-like properties. |
| title_sort | highly tumorigenic hepatocellular carcinoma cell line with cancer stem cell like properties |
| url | http://europepmc.org/articles/PMC5289561?pdf=render |
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