Cross-species hybridization of microarrays for studying tumor transcriptome of brain metastasis
Eun Sung Park ; Sun Jin Kim ; Soo Mi Kim
Yun-Yong Parka, Jae-Ho Cheonga, Hyun Goo Wooe, Gordon B. Millsa,1, Isaiah J. Fidlerb,2, and Ju-Seog Leea, ; Sang-Bae Kim ; Sun-Hee Leem ; Se-Lyun Yoon ; Seung Wook Kim
Proceedings of the National Academy of Sciences of the United States of America, Vol.108(42) : 17456~17461, 2011
Proceedings of the National Academy of Sciences of the United States of America
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.