The adaptation of colorectal cancer cells when forming metastases in the liver: expression of associated genes and pathways in a mouse model
Abstract Background Colorectal cancer (CRC) is the second leading cause of cancer-related death in men and women. Systemic disease with metastatic spread to distant sites such as the liver reduces the survival rate considerably. The aim of this study was to investigate the changes in gene expression...
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doaj-013dcd4c0472480d8a88b5a849124eb62020-11-24T21:35:02ZengBMCBMC Cancer1471-24072017-05-0117111510.1186/s12885-017-3342-1The adaptation of colorectal cancer cells when forming metastases in the liver: expression of associated genes and pathways in a mouse modelDerya Bocuk0Alexander Wolff1Petra Krause2Gabriela Salinas3Annalen Bleckmann4Christina Hackl5Tim Beissbarth6Sarah Koenig7Department of General, Visceral and Paediatric Surgery, University Medical Centre, Georg – August – University GoettingenStatistical Bioinformatics, Department of Medical Statistics, University Medical Centre, Georg – August – University GoettingenDepartment of General, Visceral and Paediatric Surgery, University Medical Centre, Georg – August – University GoettingenMicroarray and Deep-Sequencing Core Facility, Institute for Developmental Biochemistry, University Medical Centre, Georg – August – University GoettingenStatistical Bioinformatics, Department of Medical Statistics, University Medical Centre, Georg – August – University GoettingenDepartment of Surgery, University Hospital RegensburgStatistical Bioinformatics, Department of Medical Statistics, University Medical Centre, Georg – August – University GoettingenDepartment of General, Visceral and Paediatric Surgery, University Medical Centre, Georg – August – University GoettingenAbstract Background Colorectal cancer (CRC) is the second leading cause of cancer-related death in men and women. Systemic disease with metastatic spread to distant sites such as the liver reduces the survival rate considerably. The aim of this study was to investigate the changes in gene expression that occur on invasion and expansion of CRC cells when forming metastases in the liver. Methods The livers of syngeneic C57BL/6NCrl mice were inoculated with 1 million CRC cells (CMT-93) via the portal vein, leading to the stable formation of metastases within 4 weeks. RNA sequencing performed on the Illumina platform was employed to evaluate the expression profiles of more than 14,000 genes, utilizing the RNA of the cell line cells and liver metastases as well as from corresponding tumour-free liver. Results A total of 3329 differentially expressed genes (DEGs) were identified when cultured CMT-93 cells propagated as metastases in the liver. Hierarchical clustering on heat maps demonstrated the clear changes in gene expression of CMT-93 cells on propagation in the liver. Gene ontology analysis determined inflammation, angiogenesis, and signal transduction as the top three relevant biological processes involved. Using a selection list, matrix metallopeptidases 2, 7, and 9, wnt inhibitory factor, and chemokine receptor 4 were the top five significantly dysregulated genes. Conclusion Bioinformatics assists in elucidating the factors and processes involved in CRC liver metastasis. Our results support the notion of an invasion-metastasis cascade involving CRC cells forming metastases on successful invasion and expansion within the liver. Furthermore, we identified a gene expression signature correlating strongly with invasiveness and migration. Our findings may guide future research on novel therapeutic targets in the treatment of CRC liver metastasis.http://link.springer.com/article/10.1186/s12885-017-3342-1Colorectal cancer (CRC)RNA-sequencingGene expressionLiver metastasis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Derya Bocuk Alexander Wolff Petra Krause Gabriela Salinas Annalen Bleckmann Christina Hackl Tim Beissbarth Sarah Koenig |
spellingShingle |
Derya Bocuk Alexander Wolff Petra Krause Gabriela Salinas Annalen Bleckmann Christina Hackl Tim Beissbarth Sarah Koenig The adaptation of colorectal cancer cells when forming metastases in the liver: expression of associated genes and pathways in a mouse model BMC Cancer Colorectal cancer (CRC) RNA-sequencing Gene expression Liver metastasis |
author_facet |
Derya Bocuk Alexander Wolff Petra Krause Gabriela Salinas Annalen Bleckmann Christina Hackl Tim Beissbarth Sarah Koenig |
author_sort |
Derya Bocuk |
title |
The adaptation of colorectal cancer cells when forming metastases in the liver: expression of associated genes and pathways in a mouse model |
title_short |
The adaptation of colorectal cancer cells when forming metastases in the liver: expression of associated genes and pathways in a mouse model |
title_full |
The adaptation of colorectal cancer cells when forming metastases in the liver: expression of associated genes and pathways in a mouse model |
title_fullStr |
The adaptation of colorectal cancer cells when forming metastases in the liver: expression of associated genes and pathways in a mouse model |
title_full_unstemmed |
The adaptation of colorectal cancer cells when forming metastases in the liver: expression of associated genes and pathways in a mouse model |
title_sort |
adaptation of colorectal cancer cells when forming metastases in the liver: expression of associated genes and pathways in a mouse model |
publisher |
BMC |
series |
BMC Cancer |
issn |
1471-2407 |
publishDate |
2017-05-01 |
description |
Abstract Background Colorectal cancer (CRC) is the second leading cause of cancer-related death in men and women. Systemic disease with metastatic spread to distant sites such as the liver reduces the survival rate considerably. The aim of this study was to investigate the changes in gene expression that occur on invasion and expansion of CRC cells when forming metastases in the liver. Methods The livers of syngeneic C57BL/6NCrl mice were inoculated with 1 million CRC cells (CMT-93) via the portal vein, leading to the stable formation of metastases within 4 weeks. RNA sequencing performed on the Illumina platform was employed to evaluate the expression profiles of more than 14,000 genes, utilizing the RNA of the cell line cells and liver metastases as well as from corresponding tumour-free liver. Results A total of 3329 differentially expressed genes (DEGs) were identified when cultured CMT-93 cells propagated as metastases in the liver. Hierarchical clustering on heat maps demonstrated the clear changes in gene expression of CMT-93 cells on propagation in the liver. Gene ontology analysis determined inflammation, angiogenesis, and signal transduction as the top three relevant biological processes involved. Using a selection list, matrix metallopeptidases 2, 7, and 9, wnt inhibitory factor, and chemokine receptor 4 were the top five significantly dysregulated genes. Conclusion Bioinformatics assists in elucidating the factors and processes involved in CRC liver metastasis. Our results support the notion of an invasion-metastasis cascade involving CRC cells forming metastases on successful invasion and expansion within the liver. Furthermore, we identified a gene expression signature correlating strongly with invasiveness and migration. Our findings may guide future research on novel therapeutic targets in the treatment of CRC liver metastasis. |
topic |
Colorectal cancer (CRC) RNA-sequencing Gene expression Liver metastasis |
url |
http://link.springer.com/article/10.1186/s12885-017-3342-1 |
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