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Series GSE27018 Query DataSets for GSE27018
Status Public on Feb 08, 2011
Title Fibroblast triggered gene expression in tumor
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Personalized biological insights into heterogeneous tumors, such as breast cancer could improve clinical management. While genomic analysis has contributed significantly towards dissecting breast cancer heterogeneity, limitations in clinical application are partly rooted in the inter-tumor variability arising from a largely uncharacterized interactive exchange between diverse cell types in the tumor microenvironment. Here we first identified a common response signature to stromal coculture across breast cancer of varying clinicopathologic phenotypes. Proximity to fibroblasts resulted in gene transcript alterations of >2-fold for 107 probe sets, collectively designated as Fibroblast Triggered Gene Expression in Tumor (FTExT). Prominent features of tumor cell response included transcript repression related to biofunctions encompassing inflammatory signaling, cell movement, cell death, and cell growth and proliferation. In an evaluation of intertumor heterogeneity, the FTExT classifier stratified moderate and high histopathologic grade breast cancer according to clinical outcome (dataset 1, n=401, p=0.031; dataset 2, n=200, p=0.013), delineating a novel phenotype of stromal crosstalk underlying the prognostic potential of tumor grade. Extending correlative data through functional analysis of stromal-epithelial cocultures of both malignant and nonmalignant derivation, significant differences in cell cycle regulation, rate of proliferation, resistance to therapy-induced apoptosis, and growth arrest were observed in FTExT-based subgroups. Instead of a stromal impact that is uniformly cancer promoting, our data demonstrate striking variability in tumor cell response that directly contributes to contrasting functional aggressiveness of malignant breast tissue. Our findings uniquely reveal dynamically interacting paracrine components underlying the molecular and functional heterogeneity of breast cancer, thus presenting novel opportunities for tumor targeting.
 
Overall design 10 tumor samples cocultured with fibroblast were profiled in their gene expression with microarrays, and compared with 7 tumor samples cultured without fibroblast. Immortalized tumor cell lines of varying histologic grade were developed and maintained in a growth median as described in Dairkee, et al., Oncogene, 2007. In the coculture set up,
epithelial cells were seeded in 6-well plates, and fibroblasts in 0.4 μm inserts with hanging geometry (BD Biosciences, Franklin Lakes, NJ) at a 3:1 ratio in a common pool of growth medium for 3-day harvests. Controls were comprised of each epithelial sample maintained in the
absence of fibroblast-seeded inserts under the same culture conditions.
 
Contributor(s) Luciani G, Seok J, Sayeed A, Champion S, Goodson W, Xiao W, Mindrinos M, Davis RW, Dairkee SH
Citation(s) 21625507
Submission date Feb 02, 2011
Last update date Mar 25, 2019
Contact name Junhee Seok
E-mail(s) jseok@stanford.edu
Organization name Stanford University
Street address 318 Campus Drive W310 - Davis Lab
City Stanford
State/province CA
ZIP/Postal code 94305
Country USA
 
Platforms (1)
GPL570 [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array
Samples (17)
GSM665042 CCdl1797TT_none_3d
GSM665066 CCdl22TT_none_3d
GSM665067 CCdl67TT_none_3d
Relations
BioProject PRJNA137697

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE27018_RAW.tar 140.6 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table

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