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BMC Cancer. 2017 May 19;17(1):342. doi: 10.1186/s12885-017-3342-1.

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

Author information

1
Department of General, Visceral and Paediatric Surgery, University Medical Centre, Georg - August - University Goettingen, Göttingen, Germany.
2
Statistical Bioinformatics, Department of Medical Statistics, University Medical Centre, Georg - August - University Goettingen, Göttingen, Germany.
3
Microarray and Deep-Sequencing Core Facility, Institute for Developmental Biochemistry, University Medical Centre, Georg - August - University Goettingen, Göttingen, Germany.
4
Department of Haematology and Medical Oncology, University Medical Centre, Georg - August - University Goettingen, Göttingen, Germany.
5
Department of Surgery, University Hospital Regensburg, Regensburg, Germany.
6
Department of General, Visceral and Paediatric Surgery, University Medical Centre, Georg - August - University Goettingen, Göttingen, Germany. koenig_sarah@ukw.de.
7
Medical Teaching and Medical Education Research, University Hospital Wuerzburg, Julius-Maximilians-University Wuerzburg, Josef-Schneider-Str. 2/D6, 97080, Wuerzburg, Germany. koenig_sarah@ukw.de.

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.

KEYWORDS:

Colorectal cancer (CRC); Gene expression; Liver metastasis; RNA-sequencing

PMID:
28525976
PMCID:
PMC5437520
DOI:
10.1186/s12885-017-3342-1
[Indexed for MEDLINE]
Free PMC Article

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