Confrontation of fibroblasts with cancer cells in vitro: gene network analysis of transcriptome changes and differential capacity to inhibit tumor growth

• DOI: 10.1186/s13046-015-0178-x
• Publication Date: 2015-06-17T00:34:55Z
• Authors: Andrey Alexeyenko; Twana Alkasalias; Tatiana Pavlova; Laszlo Szekely; Vladimir Kashuba; Helene Rundqvist; Peter Wiklund; Lars Egevad; Peter Csermely; Tamas Korcsmaros; Hayrettin Guven; George Klein
• Keywords: 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

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.