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Newly established gastrointestinal cancer cell lines retain the genomic and immunophenotypic landscape of their parental cancers
Human cancer cell lines are frequently used as model systems to study molecular mechanisms and genetic changes in cancer. However, the model is repeatedly criticized for its lack of proximity to original patient tumors. Therefore, understanding to what extent cell lines cultured under artificial con...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578805/ https://www.ncbi.nlm.nih.gov/pubmed/33087752 http://dx.doi.org/10.1038/s41598-020-74797-0 |
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author | Hirsch, Daniela Seyfried, Steffen Staib, Tobias Fiedler, David Sauer, Christian Ried, Thomas Witt, Stephanie Rueckert, Felix Gaiser, Timo |
author_facet | Hirsch, Daniela Seyfried, Steffen Staib, Tobias Fiedler, David Sauer, Christian Ried, Thomas Witt, Stephanie Rueckert, Felix Gaiser, Timo |
author_sort | Hirsch, Daniela |
collection | PubMed |
description | Human cancer cell lines are frequently used as model systems to study molecular mechanisms and genetic changes in cancer. However, the model is repeatedly criticized for its lack of proximity to original patient tumors. Therefore, understanding to what extent cell lines cultured under artificial conditions reflect the phenotypic and genomic profiles of their corresponding parental tumors is crucial when analyzing their biological properties. To directly compare molecular alterations between patient tumors and derived cell lines, we have established new cancer cell lines from four patients with gastrointestinal tumors. Tumor entities comprised esophageal cancer, colon cancer, rectal cancer and pancreatic cancer. Phenotype and genotype of both patient tumors and derived low-passage cell lines were characterized by immunohistochemistry (22 different antibodies), array-based comparative genomic hybridization and targeted next generation sequencing (48-gene panel). The immunophenotype was highly consistent between patient tumors and derived cell lines; the expression of most markers in cell lines was concordant with the respective parental tumor and characteristic for the respective tumor entities in general. The chromosomal aberration patterns of the parental tumors were largely maintained in the cell lines and the distribution of gains and losses was typical for the respective cancer entity, despite a few distinct differences. Cancer gene mutations (e.g., KRAS, TP53) and microsatellite status were also preserved in the respective cell line derivates. In conclusion, the four examined newly established cell lines exhibited a phenotype and genotype closely recapitulating their parental tumor. Hence, newly established cancer cell lines may be useful models for further pharmacogenomic studies. |
format | Online Article Text |
id | pubmed-7578805 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-75788052020-10-23 Newly established gastrointestinal cancer cell lines retain the genomic and immunophenotypic landscape of their parental cancers Hirsch, Daniela Seyfried, Steffen Staib, Tobias Fiedler, David Sauer, Christian Ried, Thomas Witt, Stephanie Rueckert, Felix Gaiser, Timo Sci Rep Article Human cancer cell lines are frequently used as model systems to study molecular mechanisms and genetic changes in cancer. However, the model is repeatedly criticized for its lack of proximity to original patient tumors. Therefore, understanding to what extent cell lines cultured under artificial conditions reflect the phenotypic and genomic profiles of their corresponding parental tumors is crucial when analyzing their biological properties. To directly compare molecular alterations between patient tumors and derived cell lines, we have established new cancer cell lines from four patients with gastrointestinal tumors. Tumor entities comprised esophageal cancer, colon cancer, rectal cancer and pancreatic cancer. Phenotype and genotype of both patient tumors and derived low-passage cell lines were characterized by immunohistochemistry (22 different antibodies), array-based comparative genomic hybridization and targeted next generation sequencing (48-gene panel). The immunophenotype was highly consistent between patient tumors and derived cell lines; the expression of most markers in cell lines was concordant with the respective parental tumor and characteristic for the respective tumor entities in general. The chromosomal aberration patterns of the parental tumors were largely maintained in the cell lines and the distribution of gains and losses was typical for the respective cancer entity, despite a few distinct differences. Cancer gene mutations (e.g., KRAS, TP53) and microsatellite status were also preserved in the respective cell line derivates. In conclusion, the four examined newly established cell lines exhibited a phenotype and genotype closely recapitulating their parental tumor. Hence, newly established cancer cell lines may be useful models for further pharmacogenomic studies. Nature Publishing Group UK 2020-10-21 /pmc/articles/PMC7578805/ /pubmed/33087752 http://dx.doi.org/10.1038/s41598-020-74797-0 Text en © The Author(s) 2020 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Hirsch, Daniela Seyfried, Steffen Staib, Tobias Fiedler, David Sauer, Christian Ried, Thomas Witt, Stephanie Rueckert, Felix Gaiser, Timo Newly established gastrointestinal cancer cell lines retain the genomic and immunophenotypic landscape of their parental cancers |
title | Newly established gastrointestinal cancer cell lines retain the genomic and immunophenotypic landscape of their parental cancers |
title_full | Newly established gastrointestinal cancer cell lines retain the genomic and immunophenotypic landscape of their parental cancers |
title_fullStr | Newly established gastrointestinal cancer cell lines retain the genomic and immunophenotypic landscape of their parental cancers |
title_full_unstemmed | Newly established gastrointestinal cancer cell lines retain the genomic and immunophenotypic landscape of their parental cancers |
title_short | Newly established gastrointestinal cancer cell lines retain the genomic and immunophenotypic landscape of their parental cancers |
title_sort | newly established gastrointestinal cancer cell lines retain the genomic and immunophenotypic landscape of their parental cancers |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578805/ https://www.ncbi.nlm.nih.gov/pubmed/33087752 http://dx.doi.org/10.1038/s41598-020-74797-0 |
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