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Stromal microenvironment processes unveiled by biological component analysis of gene expression in xenograft tumor models.

Yang X, Lee Y, Huang Y, Chen JL, Xing RH, Lussier YA - BMC Bioinformatics (2010)

Bottom Line: We hypothesized that we could exploit the interspecies genetic differences in these experiments.By identifying cross-species hybridizing probes from sequence alignment and cross-species hybridization experiment for the human whole-genome arrays, deregulated stromal genes can be identified and then their biological significance were predicted from enrichment studies.Comparing these results with those found by the laser capture microdissection of stromal cells from tumor specimens resulted in the discovery of significantly enriched stromal biological processes.

View Article: PubMed Central - HTML - PubMed

Affiliation: Section of Genetic Medicine, Dept, of Medicine, University of Chicago, IL, USA. xyang2@uchicago.edu

ABSTRACT

Background: Mouse xenograft models, in which human cancer cells are implanted in immune-suppressed mice, have been popular for studying the mechanisms of novel therapeutic targets, tumor progression and metastasis. We hypothesized that we could exploit the interspecies genetic differences in these experiments. Our purpose is to elucidate stromal microenvironment signals from probes on human arrays unintentionally cross-hybridizing with mouse homologous genes in xenograft tumor models.

Results: By identifying cross-species hybridizing probes from sequence alignment and cross-species hybridization experiment for the human whole-genome arrays, deregulated stromal genes can be identified and then their biological significance were predicted from enrichment studies. Comparing these results with those found by the laser capture microdissection of stromal cells from tumor specimens resulted in the discovery of significantly enriched stromal biological processes.

Conclusions: Using this method, in addition to their primary endpoints, researchers can leverage xenograft experiments to better characterize the tumor microenvironment without additional costs. The Xhyb probes and R script are available at http://www.lussierlab.org/publications/Stroma.

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Related in: MedlinePlus

The network of the Xhyb enriched BP terms and two gold standards. A full network including all identified BP terms are given in Additional file 3: Suppl. Figure 1
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Figure 4: The network of the Xhyb enriched BP terms and two gold standards. A full network including all identified BP terms are given in Additional file 3: Suppl. Figure 1

Mentions: Figure 4 visualizes the graphical relationship of the identified BP terms and two gold standards (Additional file 2: S. Table 6). The biological process, “regulation of behaviour”, is of interest as a root term in 4 out of the 7 identified terms that also have overlap with GS2. This may suggest that tumor stromal actions or reactions are in response to external or internal stimuli through the regulation of chemotaxis. Note that 11 out of the 12 identified GO terms are the child nodes of the stromal gold standard terms (Additional file 3: Suppl. Figure 1).


Stromal microenvironment processes unveiled by biological component analysis of gene expression in xenograft tumor models.

Yang X, Lee Y, Huang Y, Chen JL, Xing RH, Lussier YA - BMC Bioinformatics (2010)

The network of the Xhyb enriched BP terms and two gold standards. A full network including all identified BP terms are given in Additional file 3: Suppl. Figure 1
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2967741&req=5

Figure 4: The network of the Xhyb enriched BP terms and two gold standards. A full network including all identified BP terms are given in Additional file 3: Suppl. Figure 1
Mentions: Figure 4 visualizes the graphical relationship of the identified BP terms and two gold standards (Additional file 2: S. Table 6). The biological process, “regulation of behaviour”, is of interest as a root term in 4 out of the 7 identified terms that also have overlap with GS2. This may suggest that tumor stromal actions or reactions are in response to external or internal stimuli through the regulation of chemotaxis. Note that 11 out of the 12 identified GO terms are the child nodes of the stromal gold standard terms (Additional file 3: Suppl. Figure 1).

Bottom Line: We hypothesized that we could exploit the interspecies genetic differences in these experiments.By identifying cross-species hybridizing probes from sequence alignment and cross-species hybridization experiment for the human whole-genome arrays, deregulated stromal genes can be identified and then their biological significance were predicted from enrichment studies.Comparing these results with those found by the laser capture microdissection of stromal cells from tumor specimens resulted in the discovery of significantly enriched stromal biological processes.

View Article: PubMed Central - HTML - PubMed

Affiliation: Section of Genetic Medicine, Dept, of Medicine, University of Chicago, IL, USA. xyang2@uchicago.edu

ABSTRACT

Background: Mouse xenograft models, in which human cancer cells are implanted in immune-suppressed mice, have been popular for studying the mechanisms of novel therapeutic targets, tumor progression and metastasis. We hypothesized that we could exploit the interspecies genetic differences in these experiments. Our purpose is to elucidate stromal microenvironment signals from probes on human arrays unintentionally cross-hybridizing with mouse homologous genes in xenograft tumor models.

Results: By identifying cross-species hybridizing probes from sequence alignment and cross-species hybridization experiment for the human whole-genome arrays, deregulated stromal genes can be identified and then their biological significance were predicted from enrichment studies. Comparing these results with those found by the laser capture microdissection of stromal cells from tumor specimens resulted in the discovery of significantly enriched stromal biological processes.

Conclusions: Using this method, in addition to their primary endpoints, researchers can leverage xenograft experiments to better characterize the tumor microenvironment without additional costs. The Xhyb probes and R script are available at http://www.lussierlab.org/publications/Stroma.

Show MeSH
Related in: MedlinePlus