Section of Genetic Medicine, Dept, of Medicine, University of Chicago, IL, USA.
BMC Bioinformatics. 2010 Oct 28;11 Suppl 9(Suppl 9):S11. doi: 10.1186/1471-2105-11-S9-S11.
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.
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.
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.
将人源癌细胞植入免疫抑制小鼠体内的异种移植模型，已经广泛用于研究新型治疗靶点、肿瘤进展和转移的机制。我们假设可以利用这些实验中的种间遗传差异。我们的目的是阐明来自人源芯片探针的基质微环境信号，这些探针与异种移植肿瘤模型中的鼠同源基因发生意外的杂交。
通过对人全基因组芯片进行序列比对和种间杂交实验来识别种间杂交探针，可以识别失调的基质基因，并通过富集研究预测其生物学意义。将这些结果与从肿瘤标本中分离基质细胞的激光捕获微切割结果进行比较，发现了显著富集的基质生物学过程。
使用这种方法，除了主要终点外，研究人员还可以利用异种移植实验来更好地描述肿瘤微环境，而无需额外的成本。Xhyb 探针和 R 脚本可在 http://www.lussierlab.org/publications/Stroma 上获得。
