Transcriptomics,Multiomics

Dataset Information

37

System-Wide Analysis Reveals a Complex Network of Tumor-Fibroblast Interactions Involved in Tumorigenicity


ABSTRACT: We’ve undertaken a genome-wide approach to identify and test genes in fibroblasts that are both induced upon interaction with basal breast cancer cells in culture and upregulated in stromal cells from primary human breast cancers. Several of the upregulated genes encode secreted growth factors or cytokines. Using RNAi and a co-injection tumorigenicity assay, we determined that the majority of secreted factors selected for functional validation played significant, yet functionally diverse, roles in promoting tumorigenicity. Rather than a single major mediator, these results indicate multiple points of intervention to prevent fibroblasts from supporting basal breast cancer. Additionally, we show that breast cancer subtypes differ markedly in the expression of these and other stromally secreted proteins using data from microdissected stromal samples. Induction of genes in four different fibroblast strains (HFFF2, HFF1, CCD1112Sk and Wi38) upon coculture with Cal51 and MDAMB231 human basal breast cancer cell lines. Monocultures of each group are used as the experimental control with each group having 3-4 independent biological replicates.

REANALYSED by: E-GEOD-41678

ORGANISM(S): Homo sapiens  

SUBMITTER: Scott Powers  Megha Rajaram   Jinyu Li   Mikala Egeblad    

PROVIDER: E-GEOD-41678 | ArrayExpress| 2015-08-19

SECONDARY ACCESSION(S): GSE41678PRJNA177918

REPOSITORIES: GEO, ArrayExpress

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Publications

System-wide analysis reveals a complex network of tumor-fibroblast interactions involved in tumorigenicity.

Rajaram Megha M   Li Jinyu J   Egeblad Mikala M   Powers R Scott RS  

PLoS genetics 20130919 9


Many fibroblast-secreted proteins promote tumorigenicity, and several factors secreted by cancer cells have in turn been proposed to induce these proteins. It is not clear whether there are single dominant pathways underlying these interactions or whether they involve multiple pathways acting in parallel. Here, we identified 42 fibroblast-secreted factors induced by breast cancer cells using comparative genomic analysis. To determine what fraction was active in promoting tumorigenicity, we chose  ...[more]

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