Author:
Bandapalli Obul Reddy,Kahlert Christoph,Hellstern Victoria,Galindo Luis,Schirmacher Peter,Weitz Jürgen,Brand Karsten
Abstract
Abstract
Background
Invasion-related genes over-expressed by tumor cells as well as by reacting host cells represent promising drug targets for anti-cancer therapy. Such candidate genes need to be validated in appropriate animal models.
Results
This study examined the suitability of a murine model (CT26/Balb/C) of colorectal liver metastasis to represent clinical liver metastasis specimens using a global gene expression approach. Cross-species similarity was examined between pure liver, liver invasion, tumor invasion and pure tumor compartments through overlap of up-regulated genes and gene ontology (GO)-based biological themes on the level of single GO-terms and of condensed GO-term families. Three out of four GO-term families were conserved in a compartment-specific way between the species: secondary metabolism (liver), invasion (invasion front), and immune response (invasion front and liver). Among the individual GO-terms over-represented in the invasion compartments in both species were "extracellular matrix", "cell motility", "cell adhesion" and "antigen presentation" indicating that typical invasion related processes are operating in both species. This was reflected on the single gene level as well, as cross-species overlap of potential target genes over-expressed in the combined invasion front compartments reached up to 36.5%.
Generally, histopathology and gene expression correlated well as the highest single gene overlap was found to be 44% in syn-compartmental comparisons (liver versus liver) whereas cross-compartmental overlaps were much lower (e.g. liver versus tumor: 9.7%). However, single gene overlap was surprisingly high in some cross-compartmental comparisons (e.g. human liver invasion compartment and murine tumor invasion compartment: 9.0%) despite little histolopathologic similarity indicating that invasion relevant genes are not necessarily confined to histologically defined compartments.
Conclusion
In summary, cross-species comparison on a global gene expression scale suggests the validity of an animal model representing the human situation. The actual yield of potential target genes depends on several variables including the animal model, choice of inclusion criteria, inherent species differences and histologic assessment.
Publisher
Springer Science and Business Media LLC
Reference17 articles.
1. Mueller MM, Fusenig NE: Friends or foes – bipolar effects of the tumour stroma in cancer. Nature reviews. 2004, 4 (11): 839-849.
2. Liotta LA, Kohn EC: The microenvironment of the tumour-host interface. Nature. 2001, 411 (6835): 375-379. 10.1038/35077241.
3. Bandapalli OR, Geheeb M, Kobelt D, Kuehnle K, Elezkurtaj S, Herrmann J, Gressner AM, Weiskirchen R, Beule D, Bluthgen N, Herzel H, Franke C, Brand K: Global analysis of host tissue gene expression in the invasive front of colorectal liver metastases. Int J Cancer. 2006, 118 (1): 74-89. 10.1002/ijc.21307.
4. Bandapalli OR, Schirmacher P, Brand K: Comparison of global gene expression profiles of tumor cells growing in cell culture and in vivo in the inner parts and in the invasion front of colorectal liver metastases. Pathology Research and Practice. 2006, 202 (4): 321-
5. Hlubek F, Brabletz T, Budczies J, Pfeiffer S, Jung A, Kirchner T: Heterogeneous expression of Wnt/beta-catenin target genes within colorectal cancer. Int J Cancer. 2007, 121 (9): 1941-1948. 10.1002/ijc.22916.
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