title: Global analysis of host tissue gene expression in the invasive front of colorectal liver metastases.
abstract: Host cell reactions are a crucial determinant for tumor invasion. We analyzed on a genomewide scale gene expression differences between microdissected tissues taken from unaffected liver tissue of a human colorectal tumor (LS174) growing in the livers of nude mice and tissue from the host part of the invasive front. Due to the low degree of interspecies cross-hybridization of 15% as determined on Affymetrix microarrays, our xenograft model allowed for the distinction of genes of murine versus human origin even if the respective tissues could not be isolated separately. Using the gene ontology (GO) classification, we were able to determine patterns of up- and downregulated genes in the liver part of the invasive front. We observed a pronounced overrepresentation, e.g., of the GO terms "extracellular matrix," "cell communication," "response to biotic stimulus," "structural molecule activity" and "cell growth," indicating a very pronounced host cell response to tumor invasion. On the single gene level, hepatic stellate cell (HSC) activation markers were overrepresented in the liver part of the invasion front. Immunohistochemistry and qPCR confirmed an activation of HSC as well as an increased number of HSC in the invasive front as compared to the noninvaded liver tissue. In summary, our data demonstrate the feasibility of an interspecies differential gene expression approach on a genomewide scale.
authors.affiliation: Institute of Biology, Humboldt University Berlin, Max Delbrück Center for Molecular Medicine, Berlin, Germany.
authors.forename: Obul Reddy
authors.initials: OR
authors.lastname: Bandapalli
authors.forename: Martina
authors.initials: M
authors.lastname: Geheeb
authors.forename: Dennis
authors.initials: D
authors.lastname: Kobelt
authors.forename: Katrin
authors.initials: K
authors.lastname: Kuehnle
authors.forename: Sefer
authors.initials: S
authors.lastname: Elezkurtaj
authors.forename: Jens
authors.initials: J
authors.lastname: Herrmann
authors.forename: Axel M
authors.initials: AM
authors.lastname: Gressner
authors.forename: Ralf
authors.initials: R
authors.lastname: Weiskirchen
authors.forename: Dieter
authors.initials: D
authors.lastname: Beule
authors.forename: Nils
authors.initials: N
authors.lastname: Blüthgen
authors.forename: Hanspeter
authors.initials: H
authors.lastname: Herzel
authors.forename: Claudia
authors.initials: C
authors.lastname: Franke
authors.forename: Karsten
authors.initials: K
authors.lastname: Brand
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology* / Q000556:secondary*; D000818:Animals; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology*; D015536:Down-Regulation; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000235:genetics* / Q000556:secondary*; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000235:genetics*; D016133:Polymerase Chain Reaction; D014183:Transplantation, Heterologous; D015854:Up-Regulation