Stromal microenvironment processes unveiled by biological component analysis of gene expression in xenograft tumor models.
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.
Section of Genetic Medicine, Dept, of Medicine, University of Chicago, IL, USA. xyang2@uchicago.edu
Xinan
X
Yang
Younghee
Y
Lee
Yong
Y
Huang
James L
JL
Chen
Rosie H
RH
Xing
Yves A
YA
Lussier
D000818:Animals; D003198:Computer Simulation; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism*; D014183:Transplantation, Heterologous; D059016:Tumor Microenvironment / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays