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 Mills, Isaiah J. Fidler, Ju Seog Lee

Research output: Contribution to journalArticle

63 Citations (Scopus)

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
Externally publishedYes

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Transcriptome
Brain Neoplasms
Neoplasm Metastasis
Tumor Microenvironment
Neoplasms
Cellular Microenvironment
Gene Expression
Aptitude
Neurogenesis
Epigenomics
Seeds
Soil
Brain

Keywords

  • DNA methylation
  • Genomics
  • Stromal cells
  • Tumor microenvironment

ASJC Scopus subject areas

  • General

Cite this

Cross-species hybridization of microarrays for studying tumor transcriptome of brain metastasis. / Park, Eun Sung; Kim, Sun Jin; Kim, Seung Wook; Yoon, Se Lyun; Leem, Sun Hee; Kim, Sang Bae; Kim, Soo Mi; Park, Yun Yong; Cheong, Jae Ho; Woo, Hyun Goo; Mills, Gordon; Fidler, Isaiah J.; Lee, Ju Seog.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 108, No. 42, 18.10.2011, p. 17456-17461.

Research output: Contribution to journalArticle

Park, ES, Kim, SJ, Kim, SW, Yoon, SL, Leem, SH, Kim, SB, Kim, SM, Park, YY, Cheong, JH, Woo, HG, Mills, G, Fidler, IJ & Lee, JS 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, vol. 108, no. 42, pp. 17456-17461. https://doi.org/10.1073/pnas.1114210108
Park, Eun Sung ; Kim, Sun Jin ; Kim, Seung Wook ; Yoon, Se Lyun ; Leem, Sun Hee ; Kim, Sang Bae ; Kim, Soo Mi ; Park, Yun Yong ; Cheong, Jae Ho ; Woo, Hyun Goo ; Mills, Gordon ; Fidler, Isaiah J. ; Lee, Ju Seog. / Cross-species hybridization of microarrays for studying tumor transcriptome of brain metastasis. In: Proceedings of the National Academy of Sciences of the United States of America. 2011 ; Vol. 108, No. 42. pp. 17456-17461.
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