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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Exp+Clin+Cancer+Res
2015 ; 34
(1
): 62
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Confrontation of fibroblasts with cancer cells in vitro: gene network analysis of
transcriptome changes and differential capacity to inhibit tumor growth
#MMPMID26081588
Alexeyenko A
; Alkasalias T
; Pavlova T
; Szekely L
; Kashuba V
; Rundqvist H
; Wiklund P
; Egevad L
; Csermely P
; Korcsmaros T
; Guven H
; Klein G
J Exp Clin Cancer Res
2015[Jun]; 34
(1
): 62
PMID26081588
show ga
BACKGROUND: There is growing evidence that emerging malignancies in solid tissues
might be kept under control by physical intercellular contacts with normal
fibroblasts. METHODS: Here we characterize transcriptional landscapes of
fibroblasts that confronted cancer cells. We studied four pairs of in vitro and
ex vivo fibroblast lines which, within each pair, differed in their capacity to
inhibit cancer cells. The natural process was modeled in vitro by confronting the
fibroblasts with PC-3 cancer cells. Fibroblast transcriptomes were recorded by
Affymetrix microarrays and then investigated using network analysis. RESULTS: The
network enrichment analysis allowed us to separate confrontation- and
inhibition-specific components of the fibroblast transcriptional response.
Confrontation-specific differences were stronger and were characterized by
changes in a number of pathways, including Rho, the YAP/TAZ cascade, NF-kB, and
TGF-beta signaling, as well as the transcription factor RELA. Inhibition-specific
differences were more subtle and characterized by involvement of Rho signaling at
the pathway level and by potential individual regulators such as IL6, MAPK8,
MAP2K4, PRKCA, JUN, STAT3, and STAT5A. CONCLUSIONS: We investigated the
interaction between cancer cells and fibroblasts in order to shed light on the
potential mechanisms and explain the differential inhibitory capacity of the
latter, which enabled both a holistic view on the process and details at the
gene/protein level. The combination of our methods pointed to proteins, such as
members of the Rho pathway, pro-inflammatory signature and the YAP1/TAZ cascade,
that warrant further investigation via tools of experimental perturbation. We
also demonstrated functional congruence between the in vitro and ex vivo models.
The microarray data are made available via the Gene Expression Omnibus as
GSE57199.