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Publication : Cross-species hybridization of microarrays for studying tumor transcriptome of brain metastasis.

First Author  Park ES Year  2011
Journal  Proc Natl Acad Sci U S A Volume  108
Issue  42 Pages  17456-61
PubMed ID  21987811 Mgi Jnum  J:177418
Mgi Id  MGI:5295087 Doi  10.1073/pnas.1114210108
Citation  Park ES, et al. (2011) Cross-species hybridization of microarrays for studying tumor transcriptome of brain metastasis. Proc Natl Acad Sci U S A 108(42):17456-61
abstractText  Although the importance of the cellular microenvironment (soil) during invasion and metastasis of cancer cells (seed) has been well-recognized, technical challenges have limited the ability to assess the influence of the microenvironment on cancer cells at the molecular level. Here, we show that an experimental strategy, competitive cross-species hybridization of microarray experiments, can characterize the influence of different microenvironments on cancer cells by independently extracting gene expression data of cancer and host cells when human cancer cells were xenografted into different organ sites of immunocompromised mice. Surprisingly, the analysis of gene expression data showed that the brain microenvironment induces complete reprogramming of metastasized cancer cells, resulting in a gain of neuronal cell characteristics and mimicking neurogenesis during development. We also show that epigenetic changes coincide with transcriptional reprogramming in cancer cells. These observations provide proof of principle for competitive cross-species hybridization of microarray experiments to characterize the effect of the microenvironment on tumor cell behavior.
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