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BMC Cancer
Published in: BMC Cancer 1/2017

Open Access 01-12-2017 | Research article

The adaptation of colorectal cancer cells when forming metastases in the liver: expression of associated genes and pathways in a mouse model

Authors: Derya Bocuk, Alexander Wolff, Petra Krause, Gabriela Salinas, Annalen Bleckmann, Christina Hackl, Tim Beissbarth, Sarah Koenig

Published in: BMC Cancer | Issue 1/2017

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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.
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Metadata
Title
The adaptation of colorectal cancer cells when forming metastases in the liver: expression of associated genes and pathways in a mouse model
Authors
Derya Bocuk
Alexander Wolff
Petra Krause
Gabriela Salinas
Annalen Bleckmann
Christina Hackl
Tim Beissbarth
Sarah Koenig
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2017
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-017-3342-1

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