Transcriptomics

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Transcription profiling of human primary fibroblasts from 10 anatomic sites expanded in DMEM supplemented with 10% fetal calf serum, penicillin/streptomycin, and glutamine (Tumor as Wound)


ABSTRACT: Cancer invasion and metastasis have been likened to wound healing gone awry. Despite striking parallels in cellular behavior between cancer progression and wound healing, the molecular relationships between these two processes, and their prognostic implications, are unclear. Here, based on gene expression profiles of fibroblasts from 10 anatomic sites, we identify a stereotyped gene expression program in response to serum exposure that appears to reflect the multifaceted role of fibroblasts in wound healing. The genes comprising this fibroblast common serum response are coordinately regulated in many human tumors, allowing us to identify tumors with gene expression signatures suggestive of active wounds. Genes induced in the fibroblast serum-response program are expressed in tumors by the tumor cells themselves, by tumor-associated fibroblasts, or both. The molecular features that define this wound-like phenotype can be evident at an early clinical stage, persist during treatment, and predict increased risk of metastasis and death in breast, lung, and gastric carcinomas. Thus, the transcriptional signature of the response of fibroblasts to serum links cancer progression and wound healing, and provides a powerful predictor of the clinical course in several common carcinomas. Human primary fibroblasts from 10 anatomic sites were expand in DMEM supplemented with 10% fetal calf serum, penicillin/streptomycin, and glutamine. Messenger RNA was harvested from cells 48 hours after the last media change or switch to media containing 0.1% FCS as previously described (Chang et al., 2002). Global gene expression patterns in 50 fibroblast cultures derived from 10 anatomic sites, cultured in the presence of 10% or 0.1% FBS, respectively, were characterized by DNA microarray hybridization (Chang et al., 2002).

ORGANISM(S): Homo sapiens  

SUBMITTER: Janos Demeter  Howard Chang     

PROVIDER: E-SMDB-2287 | ArrayExpress | 2005-10-31

REPOSITORIES: ArrayExpress

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Publications

Gene expression signature of fibroblast serum response predicts human cancer progression: similarities between tumors and wounds.

Chang Howard Y HY   Sneddon Julie B JB   Alizadeh Ash A AA   Sood Ruchira R   West Rob B RB   Montgomery Kelli K   Chi Jen-Tsan JT   van de Rijn Matt M   Botstein David D   Brown Patrick O PO  

PLoS biology 20040113 2


Cancer invasion and metastasis have been likened to wound healing gone awry. Despite parallels in cellular behavior between cancer progression and wound healing, the molecular relationships between these two processes and their prognostic implications are unclear. In this study, based on gene expression profiles of fibroblasts from ten anatomic sites, we identify a stereotyped gene expression program in response to serum exposure that appears to reflect the multifaceted role of fibroblasts in wo  ...[more]

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