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

Please always quote using this URN: urn:nbn:de:bvb:20-opus-170853
  • 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 ofBackground: 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.show moreshow less

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Metadaten
Author: Derya Bocuk, Alexander Wolff, Petra Krause, Gabriela Salinas, Annalen Bleckmann, Christina Hackl, Tim Beissbarth, Sarah Koenig
URN:urn:nbn:de:bvb:20-opus-170853
Document Type:Journal article
Faculties:Medizinische Fakultät / Institut für Medizinische Lehre und Ausbildungsforschung
Language:English
Parent Title (English):BMC Cancer
Year of Completion:2017
Volume:17
Issue:342
Source:BMC Cancer (2017) 17:342. DOI: 10.1186/s12885-017-3342-1
DOI:https://doi.org/10.1186/s12885-017-3342-1
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=28525976
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:RNA-sequencing; colorectal cancer (CRC); gene expression; liver metastasis
Release Date:2019/10/11
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International