title: 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.
authors: Department of Systems Biology, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
authors: Eun Sung
authors: ES
authors: Park
authors: Sun Jin
authors: SJ
authors: Kim
authors: Seung Wook
authors: SW
authors: Kim
authors: Se-Lyun
authors: SL
authors: Yoon
authors: Sun-Hee
authors: SH
authors: Leem
authors: Sang-Bae
authors: SB
authors: Kim
authors: Soo Mi
authors: SM
authors: Kim
authors: Yun-Yong
authors: YY
authors: Park
authors: Jae-Ho
authors: JH
authors: Cheong
authors: Hyun Goo
authors: HG
authors: Woo
authors: Gordon B
authors: GB
authors: Mills
authors: Isaiah J
authors: IJ
authors: Fidler
authors: Ju-Seog
authors: JS
authors: Lee
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001483:Base Sequence; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000556:secondary*; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D019175:DNA Methylation; D017931:DNA Primers / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D044127:Epigenesis, Genetic; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009474:Neurons / Q000378:metabolism; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D013045:Species Specificity; D059467:Transcriptome; D014183:Transplantation, Heterologous; D059016:Tumor Microenvironment / Q000235:genetics
chemical_list: D017931:DNA Primers; D004273:DNA, Neoplasm