Expression of genes and pathways associated with colorectal liver metastases in an orthotopic and syngeneic mouse model

Background:

Colorectal cancer (CRC) is the second most common cause of cancer-related death in men and women. Systemic disease with metastatic spread to distant sites remains a major challenge. The aim of this study was to investigate the molecular requirements necessary during the evolution of CRC cells in the liver environment.

Methods:

Cells from the CMT-93 cell line (originating from mouse CRC) were cultured in RPMI. For analysis in vivo, one million cells were injected via the portal vein into syngeneic mice livers, leading to the formation of stable metastases within three weeks. RNA of the CMT-93 cells and liver metastases as well as from matched normal liver was utilised to evaluate expression profiles of more than 20,000 genes through RNA-Seq analysis.

Results:

A total of 8,046 genes were differentially expressed when CMT-93 cells propagated in liver: 4,872 genes were up-regulated and 3,174 down-regulated. Comparing the cultured CRC cells with their liver metastases, gene expression of VEGF, STAT1, IFG1, and CXCL12 was identified as highly up-regulated, whereas vimentin, PLAUR, CCND1, and CDKN2A were down-regulated. These genes are highly relevant on crucial pathways with regard to differentiation, proliferation, and metabolic processes as determined during GO term analyses also performed.

Discussion:

Bioinformatic analysis of these RNA-Seq data may help reveal biological processes on different pathways involved during metastasis development in the liver environment. In the present study, a novel differential gene expression pattern was identified and further studies will be necessary to investigate new targets in the treatment of CRC liver metastasis.

Corresponding author: Krause, Petra

E-Mail: [e-mail]