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

Eun Sung Park, Sun Jin Kim, Seung Wook Kim, Se Lyun Yoon, Sun Hee Leem, Sang Bae Kim, Soo Mi Kim, Yun Yong Park, Jae Ho Cheong, Hyun Goo Woo, Gordon B. Mills, Isaiah J. Fidler, Ju Seog Lee

    Research output: Contribution to journalArticle

    66 Scopus citations

    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.

    Original languageEnglish (US)
    Pages (from-to)17456-17461
    Number of pages6
    JournalProceedings of the National Academy of Sciences of the United States of America
    Volume108
    Issue number42
    DOIs
    StatePublished - Oct 18 2011

    Keywords

    • DNA methylation
    • Genomics
    • Stromal cells
    • Tumor microenvironment

    ASJC Scopus subject areas

    • General

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  • Cite this

    Park, E. S., Kim, S. J., Kim, S. W., Yoon, S. L., Leem, S. H., Kim, S. B., Kim, S. M., Park, Y. Y., Cheong, J. H., Woo, H. G., Mills, G. B., Fidler, I. J., & Lee, J. S. (2011). Cross-species hybridization of microarrays for studying tumor transcriptome of brain metastasis. Proceedings of the National Academy of Sciences of the United States of America, 108(42), 17456-17461. https://doi.org/10.1073/pnas.1114210108