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


ABSTRACT: 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.

SUBMITTER: Park ES 

PROVIDER: S-EPMC3198333 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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

Park Eun Sung ES   Kim Sun Jin SJ   Kim Seung Wook SW   Yoon Se-Lyun SL   Leem Sun-Hee SH   Kim Sang-Bae SB   Kim Soo Mi SM   Park Yun-Yong YY   Cheong Jae-Ho JH   Woo Hyun Goo HG   Mills Gordon B GB   Fidler Isaiah J IJ   Lee Ju-Seog JS  

Proceedings of the National Academy of Sciences of the United States of America 20111010 42


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  ...[more]

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