Confrontation of fibroblasts with cancer cells in vitro: gene network analysis of transcriptome changes and differential capacity to inhibit tumor growth
0301 basic medicine
570
0303 health sciences
610
Cell Differentiation
Fibroblasts
In Vitro Techniques
3. Good health
03 medical and health sciences
Cell Line, Tumor
Humans
Gene Regulatory Networks
Transcriptome
Research Article
Signal Transduction
DOI:
10.1186/s13046-015-0178-x
Publication Date:
2015-06-17T00:34:55Z
AUTHORS (12)
ABSTRACT
There is growing evidence that emerging malignancies in solid tissues might be kept under control by physical intercellular contacts with normal fibroblasts.Here we characterize transcriptional landscapes of fibroblasts confronted cancer cells. We studied four pairs vitro and ex vivo fibroblast lines which, within each pair, differed their capacity to inhibit The natural process was modeled confronting the PC-3 Fibroblast transcriptomes were recorded Affymetrix microarrays then investigated using network analysis.The enrichment analysis allowed us separate confrontation- inhibition-specific components response. Confrontation-specific differences stronger characterized changes a number pathways, including Rho, YAP/TAZ cascade, NF-kB, TGF-beta signaling, as well transcription factor RELA. Inhibition-specific more subtle involvement Rho signaling at pathway level potential individual regulators such IL6, MAPK8, MAP2K4, PRKCA, JUN, STAT3, STAT5A.We interaction between cells order shed light on mechanisms explain differential inhibitory latter, which enabled both holistic view details gene/protein level. combination our methods pointed proteins, members pathway, pro-inflammatory signature YAP1/TAZ warrant further investigation via tools experimental perturbation. also demonstrated functional congruence models. microarray data are made available Gene Expression Omnibus GSE57199.
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